Gene Detail

Gene Symbol BRCA2
Synonyms BRCC2 | BROVCA2 | FACD | FAD | FAD1 | FANCD | FANCD1 | GLM3 | PNCA2 | XRCC11
Gene Description BRCA2 is a tumor suppressor involved in the homologous recombination pathway for double-strand DNA repair, thereby playing a role in genome stability (PMID: 27530658). BRCA2 germline mutations increase the risk of developing ovarian and/or breast cancer (PMID: 23364291) and somatic mutations are highest in colon, NSCLC, and ovarian cancers (PMID: 27283171).
ACMG Incidental List v2.0:
Yes, Breast-ovarian cancer, familial 2 (PMID: 27854360)
Entrez Id 675
Chromosome 13
Map Location 13q13.1
Canonical Transcript NM_000059

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
T3349A missense unknown BRCA2 T3349A does not lie within any known functional domains of the Brca2 protein (UniProt.org). T3349A has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
P3324L missense unknown BRCA2 P3324L does not lie within any known functional domains of the Brca2 protein (UniProt.org). P3324L has been identified in the scientific literature (PMID: 29126202), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
Q1782fs frameshift loss of function - predicted BRCA2 Q1782fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1782 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the nuclear localization sequence (PMID: 10570174), Q1782fs is predicted to lead to a loss of Brca2 protein function.
Y3035C missense no effect - predicted BRCA2 Y3035C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y3035C mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
K2498E missense loss of function - predicted BRCA2 K2498E lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). K2498E demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
R2494Q missense unknown BRCA2 R2494Q lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). R2494Q has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
L2865V missense no effect BRCA2 L2865V lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2865V mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138, PMID: 18451181).
T1414M missense unknown BRCA2 T1414M lies within the POLH-interacting domain of the Brca2 protein (UniProt.org). T1414M has been identified in the scientific liteature (PMID: 15744044), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
N1102Y missense unknown BRCA2 N1102Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). N1102Y has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
K2316R missense unknown BRCA2 K2316R does not lie within any known functional domains of the Brca2 protein (UniProt.org). K2316R has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
N1228D missense unknown BRCA2 N1228D lies within the BRCA2 repeat 2 of the Brca2 protein (UniProt.org). N1228D has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
A2786P missense loss of function - predicted BRCA2 A2786P lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). A2786P demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
S3058G missense no effect - predicted BRCA2 S3058G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S3058G mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
L2862P missense unknown BRCA2 L2862P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2862P demonstrates partial effect on homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
A2643G missense no effect - predicted BRCA2 A2643G lies within the SHFM1/DSS1-interacting region of the Brca2 protein (UniProt.org). A2643G mediates homology-directed DNA repair to the level comparable with wild-type Brca2 in cultured cells (PMID: 18451181) and therefore, is predicted to have no effect on Brca2 protein function.
D2679G missense no effect - predicted BRCA2 D2679G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2679G mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
V2908G missense no effect BRCA2 V2908G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). V2908G maintains chromosomal stability and rescues Brca2-null cell survival at a level comparable to wild-type Brca2 in culture (PMID: 15695382).
A2951V missense unknown BRCA2 A2951V lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). A2951V has been identified in sequencing studies (PMID: 25583476), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
S2522F missense no effect - predicted BRCA2 S2522F lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S2522F mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
Y2726C missense loss of function - predicted BRCA2 Y2726C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y2726C results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
D2611G missense loss of function - predicted BRCA2 D2611G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2611G results in decreased Brca2 activity, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
R3007G missense loss of function - predicted BRCA2 R3007G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R3007G partially reduces the homology-directed DNA repair function of Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
S3133* nonsense loss of function - predicted BRCA2 S3133* results in a premature truncation of the Brca2 protein at amino acid 3133 of 3418 (UniProt.org). S3133* has not been characterized, however, due to the effects of other truncations downstream of S3133 (PMID: 12619154, PMID: 9699678), S3133* is predicted to lead to a loss of Brca2 protein function.
I2672V missense no effect - predicted BRCA2 I2672V lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). I2672V demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
T256Kfs*19 frameshift loss of function - predicted BRCA2 T256Kfs*19 indicates a shift in the reading frame starting at amino acid 256 and terminating 19 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), T256Kfs*19 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
K1565N missense unknown BRCA2 K1565N lies within the POLH-interaction region of the Brca2 protein (UniProt.org). K1565N has been identified in the scientific literature (PMID: 16417627), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
K1690N missense unknown BRCA2 K1690N lies within the BRCA2 repeat 5 of the Brca2 protein (UniProt.org). K1690N has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
dec exp none no effect BRCA2 dec exp indicates decreased expression of the BRCA2 protein. However, the mechanism causing the decreased expression is unspecified.
F2562L missense loss of function - predicted BRCA2 F2562L lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). F2562L demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
L929S missense unknown BRCA2 L929S lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). L929S has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
N2436I missense unknown BRCA2 N2436I lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). N2436I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
V1306I missense unknown BRCA2 V1306I does not lie within any known functional domains of the Brca2 protein (UniProt.org). V1306I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
E1382D missense unknown BRCA2 E1382D lies within the POLH-interacting region of the Brca2 protein (UniProt.org). E1382D has been identified in the scientific literature (PMID: 15695382), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
S206C missense unknown BRCA2 S206C does not lie within any known functional domains of the Brca2 protein (UniProt.org). S206C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
S2509N missense no effect - predicted BRCA2 S2509N lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S2509N mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
D596H missense unknown BRCA2 D596H does not lie within any known functional domains of the Brca2 protein (UniProt.org). D596H has been identified in sequencing studies (PMID: 16284991, PMID: 18559594), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
Q3247H missense unknown BRCA2 Q3247H does not lie within any known functional domains of the Brca2 protein (UniProt.org). Q3247H has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
C1365Y missense unknown BRCA2 C1365Y lies within the POLH-interacting region of the Brca2 protein (UniProt.org). C1365Y has been identified in sequencing studies (PMID: 17924331, PMID: 19491284, PMID: 29309945), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
E919K missense unknown BRCA2 E919K lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). E919K has been identified in the scientific literature (PMID: 24504028), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
L2654P missense loss of function - predicted BRCA2 L2654P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2654P results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
E537Q missense unknown BRCA2 E537Q does not lie within any known functional domains of the Brca2 protein (UniProt.org). E537Q has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
G173C missense unknown BRCA2 G173C does not lie within any known functional domains of the Brca2 protein (UniProt.org). G173C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
loss unknown loss of function BRCA2 loss indicates loss of the BRCA2 gene, mRNA, and protein.
Y1569C missense unknown BRCA2 Y1569C lies within the POLH-interacting region of the Brca2 protein (UniProt.org). Y1569C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
S384F missense unknown BRCA2 S384F does not lie within any known functional domains of the Brca2 protein (UniProt.org). S384F has been identified in the scientific literature (PMID: 16168123), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
K1453E missense unknown BRCA2 K1453E lies within the BRCA2 repeat 3 of the Brca2 protein (UniProt.org). K1453E has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
mutant unknown unknown BRCA2 mutant indicates an unspecified mutation in the BRCA2 gene.
N289H missense unknown BRCA2 N289H does not lie within any known functional domains of the Brca2 protein (UniProt.org). N289H is a common Brca2 polymorphism (UniProt.org, PMID: 15744044), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
T582P missense loss of function - predicted BRCA2 T582P does not lie within any known functional domains of the Brca2 protein (UniProt.org). T582P confers a loss of function on Brca2 as indicated by reduced interaction with Cep55, Alix, and Tsg101 in cell culture (PMID: 22771033) and therefore, is predicted to result in a loss of Brca2 protein function.
D438Y missense unknown BRCA2 D438Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). D438Y has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
R2991H missense no effect - predicted BRCA2 R2991H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2991H mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
Y2660D missense loss of function - predicted BRCA2 Y2660D lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y2660D results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
Q2561P missense loss of function - predicted BRCA2 Q2561P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Q2561P results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
F2406L missense no effect BRCA2 F2406L lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). F2406L mediates homology-directed DNA repair and rescues Brca2-null cell survival at levels comparable to wild-type Brca2 in culture (PMID: 23108138, PMID: 22678057).
K604* nonsense loss of function - predicted BRCA2 K604* results in a premature truncation of the Brca2 protein at amino acid 640 of 3418 (UniProt.org). K604* has not been characterized, however, due to the effects of other truncations downstream of K604 (PMID: 12619154, PMID: 15695382), K604* is predicted to lead to a loss of Brca2 protein function.
Q1037* nonsense loss of function - predicted BRCA2 Q1037* results in a premature truncation of the Brca2 protein at amino acid 1037 of 3418 (UniProt.org). Due to the loss of multiple functional domains, including the DNA binding domain (UniProt.org), Q1037* is predicted to lead to a loss of function.
G2901D missense no effect BRCA2 G2901D lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2901D mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and rescued Brca1-deficient embryonic stem cells in culture at levels comparable to wild-type Brca2 (PMID: 18607349).
Q2539H missense unknown BRCA2 Q2539H lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). Q2539H has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D2723V missense loss of function - predicted BRCA2 D2723V lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). D2723V demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
D1420N missense unknown BRCA2 D1420N does not lie within any known functional domains of the Brca2 protein (UniProt.org). D1420N has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
D935N missense unknown BRCA2 D935N lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). D935N has been identified in the scientific literature (PMID: 23415752), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
L2647P missense loss of function - predicted BRCA2 L2647P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2647P results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
E2571G missense no effect - predicted BRCA2 E2571G lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). E2571G demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
A2466V missense no effect - predicted BRCA2 A2466V lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). A2466V mediates homology-directed DNA repair to the level comparable with wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
L482I missense unknown BRCA2 L482I does not lie within any known functional domains of the Brca2 protein (UniProt.org). L482I has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
R155I missense unknown BRCA2 R155I does not lie within any known functional domains of the Brca2 protein (UniProt.org). R155I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
L2587F missense no effect - predicted BRCA2 L2587F lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). L2587F demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
E456D missense unknown BRCA2 E456D does not lie within any known functional domains of the Brca2 protein (UniProt.org). E456D has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
L3180F missense unknown BRCA2 L3180F lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L3180F has been identified in the scientific literature (PMID: 22921312), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
Q2925H missense no effect - predicted BRCA2 Q2925H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Q2925H mediates homology-directed DNA repair somewhat similar to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
C554W missense loss of function - predicted BRCA2 C554W does not lie within any known functional domains of the Brca2 protein (UniProt.org). C554W results in cytokinetic defects, demonstrating increased multinucleation in cells and an elevation of unresolved cytokinetic bridges as compared to wild-type Brca2 (PMID: 22771033) and therefore, is predicted to result in a loss of Brca2 protein function.
P143S missense unknown BRCA2 P143S does not lie within any known functional domains of the Brca2 protein (UniProt.org). P143S has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
M2676T missense no effect - predicted BRCA2 M2676T lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). M2676T mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
R2973C missense no effect - predicted BRCA2 R2973C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2973C mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
R2418I missense unknown BRCA2 R2418I lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). R2418I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
G1194D missense unknown BRCA2 G1194D does not lie within any known functional domains of the Brca2 protein (UniProt.org). G1194D has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
K3326* nonsense no effect BRCA2 K3326* results in a premature truncation of the Brca2 protein at amino acid 3326 of 3418 (UniProt.org). K3326* mediates homology-directed DNA repair and rescues Brca2-null cell survival at levels comparable to wild-type Brca2 in culture (PMID: 15695382).
N1747S missense unknown BRCA2 N1747S lies within the POLH-interacting region of the Brca2 protein (UniProt.org). N1747S has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
V348L missense unknown BRCA2 V348L does not lie within any known functional domains of the Brca2 protein (UniProt.org). V348L has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
S3332Y missense unknown BRCA2 S3332Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). S3332Y has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
K2729N missense no effect - predicted BRCA2 K2729N lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). K2729N mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
G2596E missense loss of function - predicted BRCA2 G2596E lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). G2596E demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
V1643A missense unknown BRCA2 V1643A lies within the POLH-interacting region of the Brca2 protein (UniProt.org). V1643A has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
Y2997* nonsense loss of function - predicted BRCA2 Y2997* results in a premature truncation of the Brca2 protein at amino acid 2997 of 3418 (UniProt.org). Y2997* has not been characterized, however, due to the effects of other truncations downstream of Y2997 (PMID: 12619154), Y2997* is predicted to lead to a loss of Brca2 protein function.
negative unknown unknown BRCA2 negative indicates a lack of the BRCA2 gene, mRNA, and/or protein.
C1265S missense unknown BRCA2 C1265S does not lie within any known functional domains of the Brca2 protein (UniProt.org). C1265S has been identified in the scientific literature (PMID: 16489001), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
L2972W missense unknown BRCA2 L2972W lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2972W demonstrates partial effect on homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
P168T missense unknown BRCA2 P168T does not lie within any known functional domains of the Brca2 protein (UniProt.org). P168T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
F2642S missense loss of function - predicted BRCA2 F2642S lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). F2642S demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
G2793E missense loss of function - predicted BRCA2 G2793E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2793E results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
R18H missense unknown BRCA2 R18H lies within the PALB2-interacting region of the Brca2 protein (UniProt.org). R18H has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
T1785I missense unknown BRCA2 T1785I does not lie within any known functional domains of the Brca2 protein (UniProt.org). T1785I has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A2603P missense loss of function - predicted BRCA2 A2603P lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). A2603P results in decreased homology-directed DNA repair activity in culture (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
G1529R missense unknown BRCA2 G1529R lies within the BRCA2 repeat 4 of the Brca2 protein (UniProt.org). G1529R has been identified in the scientific literature (PMID: 23071527, PMID: 20104584), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
R2659K missense loss of function BRCA2 R2659K lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2659K results in decreased homology-directed DNA repair, increased chromosomal instability, and is unable to rescue Brca2-null cell survival in culture (PMID: 15695382).
R2108H missense no effect - predicted BRCA2 R2108H does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2108H has been described as non-pathogenic and like wild-type Brca2, is not sensitive to DNA damaging agents and has no effect on splicing or homologous recombination (PMID: 22678057) and therefore, is predicted to have no effect on Brca2 protein function.
L2688P missense loss of function - predicted BRCA2 L2688P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2688P results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
D2723G missense loss of function - predicted BRCA2 D2723G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2723G results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
K2411T missense no effect - predicted BRCA2 K2411T lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). K2411T mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
L2080* nonsense loss of function - predicted BRCA2 L2080* results in a premature truncation of the Brca2 protein at amino acid 2080 of 3418 (UniProt.org). Due to the loss of multiple functional domains, including the DNA binding domain (UniProt.org), L2080* is predicted to lead to a loss Brca2 protein function.
Q2925K missense loss of function - predicted BRCA2 Q2925K lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Q2925K results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
L1904V missense unknown BRCA2 L1904V does not lie within any known functional domains of the Brca2 protein (UniProt.org). L1904V has been identified in the scientific literature (PMID: 15744044), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
S869L missense unknown BRCA2 S869L lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). S869L has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
R2502C missense unknown BRCA2 R2502C lies within the FANCD2 and SEM1-interacting regions of the Brca2 protein (UniProt.org). R2502C has been identified in the scientific literature (PMID: 10882858), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
P288S missense unknown BRCA2 P288S does not lie within any known functional domains of the Brca2 protein (UniProt.org). P288S has been identified in sequencing studies (PMID: 17088437), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
G2837E missense unknown BRCA2 G2837E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2837E demonstrates partial effect on homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
T630I missense unknown BRCA2 T630I does not lie within any known functional domains of the Brca2 protein (UniProt.org). T630I has been identified in sequencing studies (PMID: 28591191), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
W2725L missense loss of function - predicted BRCA2 W2725L lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). W2725L results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
K607T missense unknown BRCA2 K607T does not lie within any known functional domains of the Brca2 protein (UniProt.org). K607T has been identified in the scientific literature (PMID: 18375895), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
N2048I missense unknown BRCA2 N2048I does not lie within any known functional domains of the Brca2 protein (UniProt.org). N2048I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
V3365_S3366insVNYI insertion unknown BRCA2 V3365_S3366insVNYI results in the insertion of four amino acids in the Brca2 protein between amino acids 3365 and 3366 (UniProt.org). V3365_S3366insVNYI has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
R2488T missense unknown BRCA2 R2488T lies within the FANCD2 and SEM1-interacting region of the Brca2 protein (UniProt.org). R2488T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
K513R missense unknown BRCA2 K513R does not lie within any known functional domains of the Brca2 protein (UniProt.org). K513R has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
E1285fs frameshift loss of function - predicted BRCA2 E1285fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1285 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). E1285fs has not been characterized, however, due to the effects of other truncations downstream of E1285 (PMID: 12619154, PMID: 15695382), E1285fs is predicted to lead to a loss of Brca2 protein function.
S2695L missense no effect BRCA2 S2695L lies within the SHFM1/DSS1 interaction region of the Brca2 protein (UniProt.org). S2695L demonstrates DNA repair activity and rescue of lethality of Brca-null embryonic stem cells to a similar level to wild-type Brca2 in culture (PMID: 22678057).
I2821T missense no effect - predicted BRCA2 I2821T lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). I2821T demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
R2488G missense no effect - predicted BRCA2 R2488G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2488G mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
E3002K missense loss of function BRCA2 E3002K lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). E3002K results in decreased homology-directed DNA repair and is unable to rescue Brca2-null cell survival in culture (PMID: 23108138, PMID: 22678057).
E1879D missense unknown BRCA2 E1879D does not lie within any known functional domains of the Brca2 protein (UniProt.org). E1879D has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
N255Tfs*21 frameshift loss of function - predicted BRCA2 N255Tfs*21 indicates a shift in the reading frame starting at amino acid 255 and terminating 21 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), N255Tfs*21 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
N372H missense unknown BRCA2 N372H does not lie within any known functional domains of the Brca2 protein (UniProt.org). N372H is conflicting, as it rescues Brca2-null cell survival at a level comparable to wild-type Brca2 in culture (PMID: 15695382), but demonstrated altered histone acetyltransferase activity in an in vitro assay (PMID: 28431939).
E3071D missense no effect - predicted BRCA2 E3071D lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). E3071D demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
N272Kfs*2 frameshift loss of function - predicted BRCA2 N272Kfs*2 indicates a shift in the reading frame starting at amino acid 272 and terminating 2 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), N272Kfs*2 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
R3052Q missense no effect BRCA2 R3052Q does not lie within any known functional domains of the Brca2 protein (UniProt.org). R3052Q has no effect on cell viability and does not affect genomic stability in culture (PMID: 18607349).
T1354A missense unknown BRCA2 T1354A lies within the POLH-interacting region of the Brca2 protein (UniProt.org). T1354A has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
W2626C missense loss of function BRCA2 W2626C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). W2626C results in decreased Brca2 function, indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and failed to rescue Brca2-deficient embryonic stem cells in culture (Cancer Res 2011;71(8 Suppl):Abstract nr 228).
E2757V missense no effect - predicted BRCA2 E2757V lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). E2757V demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
S2616C missense unknown BRCA2 S2616C lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). S2616C has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
G2584D missense no effect - predicted BRCA2 G2584D lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). G2584D demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
Q2655R missense loss of function - predicted BRCA2 Q2655R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Q2655R results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
S2704F missense unknown BRCA2 S2704F lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S2704F has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
D1420Y missense no effect - predicted BRCA2 D1420Y lies within the POLH-interacting region of the Brca2 protein (UniProt.org). D1420Y demonstrates cell viability by rescuing Brca1-deficient embryonic stem cells in culture (PMID: 18607349), and therefore, is predicted to have no effect on Brca2 protein function.
I1607S missense unknown BRCA2 I1607S lies within the POLH-interacting region of the Brca2 protein (UniProt.org). I1607S has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
W2788S missense loss of function - predicted BRCA2 W2788S lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). W2788S results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
G2063E missense unknown BRCA2 G2063E lies within the BRCA2 repeat 8 of the Brca2 protein (UniProt.org). G2063E has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
K2630Q missense loss of function - predicted BRCA2 K2630Q lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). K2630Q demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
N3124I missense loss of function BRCA2 N3124I lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). N3124I results in decreased homology-directed DNA repair and is unable to rescue Brca2-null cell survival in culture (PMID: 23108138, PMID: 22678057).
S1424C missense unknown BRCA2 S1424C lies within the POLH-interacting region of the Brca2 protein (UniProt.org). S1424C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
P3039L missense no effect BRCA2 P3039L lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). P3039L mediates splicing and homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23451180, PMID: 29394989).
I1017F missense unknown BRCA2 I1017F lies within the BRCA2 repeat 1 of the Brca2 protein (UniProt.org). I1017F has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
P3063S missense no effect - predicted BRCA2 P3063S lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). P3063S mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
N1642T missense unknown BRCA2 N1642T lies within the POLH-interacting region of the Brca2 protein (UniProt.org). N1642T has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D2723A missense loss of function - predicted BRCA2 D2723A lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2723A results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
K2950N missense unknown BRCA2 K2950N does not lie within any known functional domains of the Brca2 protein (UniProt.org). K2950N has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
Q2858R missense unknown BRCA2 Q2858R does not lie within any known functional domains of the Brca2 protein (UniProt.org). Q2858R has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
L2510P missense loss of function BRCA2 L2510P lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). L2510P results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and demonstrated defective RAD51 foci formation following irradiation treatment in culture (PMID: 21719596).
R2418G missense unknown BRCA2 R2418G lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). R2418G has been identified in the scientific literature (PMID: 18824701), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
E2020K missense unknown BRCA2 E2020K does not lie within any known functional domains of the Brca2 protein (UniProt.org). E2020K has been identified in sequencing studies (PMID: 11698567), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D2723H missense loss of function BRCA2 D2723H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2723H results in decreased homology-directed DNA repair, increased chromosomal instability, and is unable to rescue Brca2-null cell survival in culture (PMID: 23108138, PMID: 15695382).
D244Efs*10 frameshift loss of function - predicted BRCA2 D244Efs*10 indicates a shift in the reading frame starting at amino acid 244 and terminating 10 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), D244Efs*10 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
L2653P missense loss of function - predicted BRCA2 L2653P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2653P results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
Y3035S missense no effect - predicted BRCA2 Y3035S lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y3035S mediates homology-directed DNA repair somewhat similar to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
H1918Y missense unknown BRCA2 H1918Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). H1918Y has been identified in the scientific literature (PMID: 28866612), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
N257Kfs*17 frameshift loss of function - predicted BRCA2 N257Kfs*17 indicates a shift in the reading frame starting at amino acid 257 and terminating 17 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), N257Kfs*17 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
D3073G missense loss of function - predicted BRCA2 D3073G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D3073G results in decreased Brca2 function, indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
S3020C missense no effect - predicted BRCA2 S3020C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S3020C mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
P2800R missense loss of function - predicted BRCA2 P2800R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). P2800R results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
S278N missense unknown BRCA2 S278N does not lie within any known functional domains of the Brca2 protein (UniProt.org). S278N has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
R2784Q missense loss of function - predicted BRCA2 R2784Q lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2784Q results in decreased Brca2 function, as indicated by decreased homology directed recombination in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
T1887M missense unknown BRCA2 T1887M does not lie within any known functional domains of the Brca2 protein (UniProt.org). T1887M has been identified in the scientific literature (PMID: 15172753) but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A1981S missense unknown BRCA2 A1981S lies within the BRCA2 repeat 7 of the Brca2 protein (UniProt.org). A1981S has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
R2336P missense unknown BRCA2 R2336P does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2336P has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
I2944F missense no effect BRCA2 I2944F does not lie within any known functional domains of the Brca2 protein (UniProt.org). I2944F demonstrates DNA repair activity and rescue of BRCA null ES cells to similar level of wild-type Brca2 in culture (PMID: 22678057).
R2842H missense unknown BRCA2 R2842H does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2842H has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
Y2660C missense unknown BRCA2 Y2660C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y2660C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
G3003E missense loss of function - predicted BRCA2 G3003E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G3003E demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
A2711T missense unknown BRCA2 A2711T lies within the SEM1-interacting region and DNA-binding domain of the Brca2 protein (PMID: 12228710, UniProt.org). A2711T has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
G2508S missense unknown BRCA2 G2508S lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). G2508S has been identified in the scientific literature (PMID: 28283652), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
R2520Q missense no effect - predicted BRCA2 R2520Q lies within the SHFM1/DSS1-interacting region of the Brca2 protein (UniProt.org). R2520Q mediates homology-directed DNA repair to the level comparable with wild type Brca2 in cultured cells (PMID: 18451181) and therefore, is predicted to have no effect on Brca2 protein function.
E2476* nonsense loss of function - predicted BRCA2 E2476* results in a premature truncation of the Brca2 protein at amino acid 2476 of 3418 (UniProt.org). E2476* has not been characterized, however, due to the effects of other truncations downstream of E2476 (PMID: 12619154, PMID: 9699678), E2476* is predicted to lead to a loss of Brca2 protein function.
A2233T missense unknown BRCA2 A2233T does not lie within any known functional domains of the Brca2 protein (UniProt.org). A2233T has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
I2285V missense no effect BRCA2 I2285V does not lie within any known functional domains of the Brca2 protein (UniProt.org). I2285V confers no effect on the Brca2 protein as demonstrated by homology-directed DNA repair and induced RAD51 formation foci similar to Brca2 wild-type levels (PMID: 19795481).
V1078I missense unknown BRCA2 V1078I does not lie within any known functional domains of the Brca2 protein (UniProt.org). V1078I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
D2679Y missense no effect - predicted BRCA2 D2679Y lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2679Y mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
G3076E missense loss of function BRCA2 G3076E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G3076E results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138).
S2691F missense loss of function - predicted BRCA2 S2691F lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S2691F results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
G602R missense unknown BRCA2 G602R does not lie within any known functional domains of the Brca2 protein (UniProt.org). G602R has been identified in the scientific literature (PMID: 21218378), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
S2988G missense no effect BRCA2 S2988G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S2988G mediates splicing and homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 21735045, PMID: 29394989) and rescued Brca1-deficient embryonic stem cells in culture, demonstrating cell viability (PMID: 18607349).
T1302del deletion loss of function BRCA2 T1302del results in the deletion of an amino acid within the BRC repeats of the Brca2 protein at amino acid 1302 (PMID: 15695382). T1302del results in increased chromosomal instability and is unable to rescue Brca2-null cell survival in culture (PMID: 15695382).
L2581W missense no effect - predicted BRCA2 L2581W lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). L2581W demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
N1742I missense unknown BRCA2 N1742I lies within the POLH-interacting region of the Brca2 protein (UniProt.org). N1742I has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
P365Q missense unknown BRCA2 P365Q does not lie within any known functional domains of the Brca2 protein (UniProt.org). P365Q has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
E510* nonsense loss of function - predicted BRCA2 E510* results in a premature truncation of the Brca2 protein at amino acid 510 of 3418 (UniProt.org). E510* has not been characterized, however, due to the effects of other truncations downstream of E510 (PMID: 12619154, PMID: 15695382), E510* is predicted to lead to a loss of Brca2 protein function.
P2734H missense unknown BRCA2 P2734H lies within the SEM1-interacting region of the Brca2 protein (Uniprot.org). P2734H has been identified in sequencing studies (PMID: 25583476), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
I605fs frameshift loss of function - predicted BRCA2 I605fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 605 of 3418 (UniProt.org). Due to the loss of multiple functional domains (UniProt.org), I605fs is predicted to lead to a loss of Brca2 protein function.
R2659G missense loss of function BRCA2 R2659G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2659G results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138).
R2787H missense no effect - predicted BRCA2 R2787H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2787H mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
Q2384K missense unknown BRCA2 Q2384K lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). Q2384K has been identified in the scientific literature (PMID: 15744044), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
S3319Y missense unknown BRCA2 S3319Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). S3319Y has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A2770T missense unknown BRCA2 A2770T lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). A2770T has been identified in the scientific literature (PMID: 21990165, PMID: 16489001), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
K2472T missense unknown BRCA2 K2472T lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). K2472T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
G1771D missense unknown BRCA2 G1771D lies within the POLH-interacting region of the Brca2 protein (UniProt.org). G1771D has been identified in the scientific literature (PMID: 28425764, PMID: 18431501), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
R2888C missense unknown BRCA2 R2888C does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2888C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
I2672fs frameshift loss of function - predicted BRCA2 I2672fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 2672 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). I2672fs has not been characterized, however, due to the effects of other truncations downstream of I2672 (PMID: 12619154), I2672fs is predicted to lead to a loss of Brca2 protein function.
M784V missense unknown BRCA2 M784V lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). M784V has been identified in the scientific literature (PMID: 18824701), but has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
V2652M missense no effect - predicted BRCA2 V2652M lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). V2652M mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
K2017T missense unknown BRCA2 K2017T does not lie within any known functional domains of the Brca2 protein (UniProt.org). K2017T has been identified in the scientific literature (PMID: 28591715), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
S2483N missense unknown BRCA2 S2483N lies within the FANCD2 and SEM1-interacting region of the Brca2 protein (UniProt.org). S2483N has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
L209F missense unknown BRCA2 L209F does not lie within any known functional domains of the Brca2 protein (UniProt.org). L209F has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
F1192C missense unknown BRCA2 F1192C does not lie within any known functional domains of the Brca2 protein (UniProt.org). F1192C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
S1172L missense unknown BRCA2 S1172L does not lie within any known functional domains of the Brca2 protein (UniProt.org). S1172L has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
I2675V missense unknown BRCA2 I2675V lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). I2675V has been identified in the scientific literature (PMID: 26439132), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
T868I missense unknown BRCA2 T868I lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). T868I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
E49* nonsense loss of function - predicted BRCA2 E49* results in a premature truncation of the Brca2 protein at amino acid 49 of 3418 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), E49* is predicted to lead to a loss of Brca2 protein function.
N1784fs missense loss of function - predicted BRCA2 N1784fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1784 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the nuclear localization sequence (PMID: 10570174), N1784fs is predicted to lead to a loss of Brca2 protein function.
N56T missense unknown BRCA2 N56T does not lie within any known functional domains of the Brca2 protein (UniProt.org). N56T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
E2663V missense loss of function BRCA2 E2663V lies within the SHFM1/DSS1-interacting region of the Brca2 protein (UniProt.org). E2663V results in aberrant splicing and introduction of a premature stop codon (PMID: 18451181) and failed to rescue Brca2-deficient embryonic stem cells in culture (PMID: 18607349).
del deletion loss of function BRCA2 del indicates a deletion of the BRCA2 gene.
N257Efs*19 frameshift loss of function - predicted BRCA2 N257Efs*19 indicates a shift in the reading frame starting at amino acid 257 and terminating 19 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), N257Efs*19 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
D806H missense unknown BRCA2 D806H lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). D806H has been identified in sequencing studies (PMID: 17924331), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
S326R missense unknown BRCA2 S326R does not lie within any known functional domains of the Brca2 protein (UniProt.org). S326R has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
K1691fs frameshift loss of function - predicted BRCA2 K1691fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1691 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). K1691fs has not been characterized, however, due to the effects of other truncations downstream of K1691 (PMID: 12619154, PMID: 15695382), K1691fs is predicted to lead to a loss of Brca2 protein function.
E897* nonsense loss of function - predicted BRCA2 E897* results in a premature truncation of the Brca2 protein at amino acid 897 of 3418 (UniProt.org). E897* has not been characterized, however, due to the effects of other truncations downstream of E897 (PMID: 12619154, PMID: 15695382), E897* is predicted to lead to a loss of Brca2 protein function.
K1649I missense unknown BRCA2 K1649I lies within the POLH-interaction region of the Brca2 protein (UniProt.org). K1649I has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D2665G missense no effect - predicted BRCA2 D2665G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2665G mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
S2243Y missense unknown BRCA2 S2243Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). S2243Y has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
D2913E missense no effect - predicted BRCA2 D2913E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2913E demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
D1352Y missense unknown BRCA2 D1352Y lies within the POLH-interacting region of the Brca2 protein (UniProt.org). D1352Y has been identified in the scientific literature (PMID: 21990165), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
Q1396R missense unknown BRCA2 Q1396R lies within the POLH-interacting region of the Brca2 protein (UniProt.org). Q1396R has been identified in the scientific literature (PMID: 22034289), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
C1200fs frameshift loss of function - predicted BRCA2 C1200fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1200 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). C1200fs has not been characterized, however, due to the effects of other truncations downstream of C1200 (PMID: 12619154, PMID: 15695382), C1200fs is predicted to lead to a loss of Brca2 protein function.
D3170G missense no effect - predicted BRCA2 D3170G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D3170G mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
G1761V missense unknown BRCA2 G1761V lies within the POLH-interacting region of the Brca2 protein (UniProt.org). G1761V has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
G2748D missense loss of function - predicted BRCA2 G2748D lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2748D results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
G2585R missense loss of function - predicted BRCA2 G2585R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2585R results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
P655R missense no effect - predicted BRCA2 P655R does not lie within any known functional domains of the Brca2 protein (UniProt.org). P655R has been described as non-pathogenic and like wild-type Brca2, is not sensitive to DNA damaging agents and has no effect on splicing or homologous recombination (PMID: 22678057) and therefore, is predicted to have no effect on Brca2 protein function.
Y42C missense loss of function BRCA2 Y42C does not lie within any known functional domains of the Brca2 protein (UniProt.org). Y42C results in decreased homology-directed DNA repair and is unable to rescue Brca2-null cell survival in culture (PMID: 15695382).
S1064* nonsense loss of function - predicted BRCA2 S1064* results in a premature truncation of the Brca2 protein at amino acid 1064 of 3418 (UniProt.org). S1064* has not been characterized, however, due to the effects of other truncations downstream of S1064 (PMID: 12619154, PMID: 15695382), S1064* is predicted to lead to a loss of Brca2 protein function.
E2229* nonsense loss of function - predicted BRCA2 E2229* results in a premature truncation of the Brca2 protein at amino acid 2229 of 3418 (UniProt.org). E2229* has not been characterized, however, due to the effects of other truncations downstream of E2229 (PMID: 12619154, PMID: 9699678), E2229* is predicted to lead to a loss of Brca2 protein function.
S2807L missense no effect - predicted BRCA2 S2807L lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S2807L mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
R2784W missense loss of function - predicted BRCA2 R2784W lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2784W results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
N2113S missense unknown BRCA2 N2113S does not lie within any known functional domains of the Brca2 protein (UniProt.org). N2113S has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
A2951T missense no effect BRCA2 A2951T lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). A2951T mediates homology-directed DNA repair to the level comparable with wild-type Brca2 in cultured cells (PMID: 23108138, PMID: 23328489).
R2842C missense loss of function - predicted BRCA2 R2842C does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2842C results in decreased Brca1 activity, as indicated by decreased homology directed recombination in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
E3002L missense loss of function - predicted BRCA2 E3002L lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). E3002L demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
H1350N missense unknown BRCA2 H1350N lies within the POLH-interacting region of the Brca2 protein (UniProt.org). H1350N has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
H1752Y missense unknown BRCA2 H1752Y lies within the POLH-interacting region of the Brca2 protein (UniProt.org). H1752Y has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D479Y missense unknown BRCA2 D479Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). D479Y has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
L2792P missense loss of function - predicted BRCA2 L2792P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2792P results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
P2639A missense no effect - predicted BRCA2 P2639A lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). P2639A mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
S1982fs frameshift loss of function - predicted BRCA2 S1982fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1982 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). S1982fs has not been characterized, however, due to the effects of other truncations downstream of S1982 (PMID: 12619154, PMID: 15695382), S1982fs is predicted to lead to a loss of Brca2 protein function.
R2488S missense no effect - predicted BRCA2 R2488S lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2488S mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
E2258K missense unknown BRCA2 E2258K does not lie within any known functional domains of the Brca2 protein (UniProt.org). E2258K has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
inact mut unknown loss of function BRCA2 inact mut indicates that this variant results in a loss of function of the Brca2 protein. However, the specific amino acid change has not been identified.
R2678G missense no effect - predicted BRCA2 R2678G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2678G mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
Q699H missense unknown BRCA2 Q699H lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). Q699H has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
wild-type none no effect Wild-type BRCA2 indicates that no mutation has been detected within the BRCA2 gene.
S3016Y missense unknown BRCA2 S3016Y lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S3016Y has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
R174C missense unknown BRCA2 R174C does not lie within any known functional domains of the Brca2 protein (UniProt.org). R174C has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
T3013I missense no effect - predicted BRCA2 T3013I lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). T3013I mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
S2670L missense unknown BRCA2 S2670L lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). S2670L has not been identified in the scientific literature (PMID: 22895246), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
L2721H missense loss of function - predicted BRCA2 L2721H lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). L2721H results in decreased homology-directed DNA repair in cultured cells (PMID: 19043619) and therefore, is predicted to result in a loss of Brca2 protein function.
I247Kfs*2 frameshift loss of function - predicted BRCA2 I247Kfs*2 indicates a shift in the reading frame starting at amino acid 247 and terminating 2 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), I247Kfs*2 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
S2782N missense no effect - predicted BRCA2 S2782N lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S2782N mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
S142I missense unknown BRCA2 S142I does not lie within any known functional domains of the Brca2 protein (UniProt.org). S142I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
K2849E missense no effect - predicted BRCA2 K2849E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). K2849E demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
E3002D missense loss of function BRCA2 E3002D lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). E3002D results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and leads to decreased interaction with Filamin A actin-binding protein, subsequently resulting in cytokinetic impairment (PMID: 22771033).
E350* nonsense loss of function - predicted BRCA2 E350* results in a premature truncation of the Brca2 protein at amino acid 350 of 3418 (UniProt.org). E350* has not been characterized, however, due to the effects of other truncations downstream of E350 (PMID: 12619154, PMID: 15695382), E350* is predicted to lead to a loss of Brca2 protein function.
I1772S missense unknown BRCA2 I1772S lies within the POLH-interaction region of the Brca2 protein (UniProt.org). I1772S has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
R2318Q missense loss of function - predicted BRCA2 R2318Q does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2318Q is predicted to lead to a loss of Brca2 protein function as indicated by loss of DNA damage repair activity in cultured cells over expressing a peptide of the Brca2 linker region containing R2318Q (PMID: 21741379).
E3152K missense no effect - predicted BRCA2 E3152K lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). E3152K demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
L3125H missense loss of function BRCA2 L3125H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L3125H results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989).
A2632G missense no effect - predicted BRCA2 A2632G lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). A2632G demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
P3194Q missense unknown BRCA2 P3194Q lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). P3194Q has not been characterized, but is predicted to disrupt Brca2 binding to Cdk2 in computational models (PMID: 23704879).
T2722R missense loss of function BRCA2 T2722R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). T2722R results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and demonstrates aberrant splicing in in vitro assays (PMID: 12145750, PMID: 18607349) and failed to rescue Brca2-deficient embryonic stem cells in culture (PMID: 18607349).
P606L missense unknown BRCA2 P606L does not lie within any known functional domains of the Brca2 protein (UniProt.org). P606L has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D191G missense unknown BRCA2 D191G does not lie within any known functional domains of the Brca2 protein (UniProt.org). D191G has been identified in the scientific literature (PMID: 22962691), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
R2645fs frameshift loss of function - predicted BRCA2 R2645fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 2645 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). R2645fs has not been characterized, however, due to the effects of other truncations downstream of R2645 (PMID: 12619154, PMID: 9699678), R2645fs is predicted to lead to a loss of Brca2 protein function.
H2074N missense unknown BRCA2 H2074N lies within the BRCA2 repeat 8 of the Brca2 protein (UniProt.org). H2074N has been identified in sequencing studies (PMID: 22034289), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
S1680Y missense unknown BRCA2 S1680Y lies within the POLH-interacting region of the Brca2 protein (UniProt.org). S1680Y has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
T1354M missense unknown BRCA2 T1354M lies within the POLH-interacting region of the Brca2 protein (UniProt.org). T1354M has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
R3384Q missense unknown BRCA2 R3384Q does not lie within any known functional domains of the Brca2 protein (UniProt.org). R3384Q has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
I247_E254del deletion unknown BRCA2 I247_E254del results in the deletion of 8 amino acids in the Brca2 protein (UniProt.org). I247_E254del has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
V211I missense loss of function BRCA2 V211I does not lie within any known functional domains of the Brca2 protein (UniProt.org). V211I confers a loss of function on Brca2 as indicated by an alteration in RNA splicing and reduced mRNA maturation (PMID: 19179552).
V3079I missense unknown BRCA2 V3079I does not lie within any known functional domains of the Brca2 protein (UniProt.org). V3079I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
N1878K missense no effect - predicted BRCA2 N1878K does not lie within any known functional domains of the Brca2 protein (UniProt.org). N1878K mediates homology-directed DNA repair to the level comparable with wild-type Brca2 in cultured cells (PMID: 23328489) and therefore, is predicted to have no effect on Brca2 protein function.
S2216F missense unknown BRCA2 S2216F does not lie within any known functional domains of the Brca2 protein (UniProt.org). S2216F has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
N136Ifs*16 frameshift loss of function - predicted BRCA2 N136Ifs*16 likely results in a truncation of the 3418 aa Brca2 protein at aa 136, followed by 16 nonsense amino acids (UniProt.org). N136Ifs*16 has not been characterized, however, due to the effects of other truncations downstream of N136 (PMID: 12619154, PMID: 15695382), N136Ifs*16 is predicted to lead to a loss of Brca2 protein function.
R2845fs frameshift loss of function - predicted BRCA2 R2845fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 2845 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). R2845fs has not been characterized, however, due to the effects of other truncations downstream of R2845 (PMID: 12619154), R2845fs is predicted to lead to a loss of Brca2 protein function.
S196I missense unknown BRCA2 S196I does not lie within any known functional domains of the Brca2 protein (UniProt.org). S196I has not been characterized, but via in silico analysis, is predicted to disrupt Brca2 interaction with P/Caf via altering conserved phosphorylation motifs (PMID: 23704879).
T3195A missense unknown BRCA2 T3195A does not lie within any known functional domains of the Brca2 protein (UniProt.org). T3195A has been identified in sequencing studies (PMID: 16905680), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
G2793R missense loss of function - predicted BRCA2 G2793R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2793R results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
K1434I missense unknown BRCA2 K1434I lies within the POLH-interacting region of the Brca2 protein (UniProt.org). K1434I has been identified in the scientific literature (PMID: 27797976), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
E2856A missense no effect - predicted BRCA2 E2856A lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). E2856A mediates homology-directed DNA repair at a level comparable with wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
F1524V missense unknown BRCA2 F1524V lies within the BRCA2 repeat 4 of the Brca2 protein (UniProt.org). F1524V has been identified in sequencing studies (PMID: 25344691, PMID: 22666503), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
T1673P missense unknown BRCA2 T1673P lies within the POLH1-interacting domain of the Brca2 protein (UniProt.org). T1673P has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A2717S missense no effect BRCA2 A2717S lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). A2717S results in the rescue of Brca2-deficient mouse embryonic stem cells in vitro and demonstrates homologous repair activity similar to Brca2 wild-type (PMID: 28283652).
H1966Y missense unknown BRCA2 H1966Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). H1966Y has been identified in the scientific literature (PMID: 18824701), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
I332F missense unknown BRCA2 I332F does not lie within any known functional domains of the Brca2 protein (UniProt.org). I332F has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
K1180R missense unknown BRCA2 K1180R does not lie within any known functional domains of the Brca2 protein (UniProt.org). K1180R has been identified in the scientific literature (PMID: 10882858), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D3095E missense loss of function BRCA2 D3095E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D3095E results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138, PMID: 18451181).
G2609D missense loss of function - predicted BRCA2 G2609D lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2609D results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
N243Kfs*3 frameshift loss of function - predicted BRCA2 N243Kfs*3 indicates a shift in the reading frame starting at amino acid 243 and terminating 3 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), N243Kfs*3 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
V3365fs frameshift unknown BRCA2 V3365fs results in a change in the amino acid sequence of the Brca2 protein beginning at 3365 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). V3365fs has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
G2274V missense unknown BRCA2 G2274V does not lie within any known functional domains of the Brca2 protein (UniProt.org). G2274V has been identified in the scientific literature (PMID: 16489001), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
E260Sfs*15 frameshift loss of function - predicted BRCA2 E260Sfs*15 indicates a shift in the reading frame starting at amino acid 260 and terminating 15 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), E260Sfs*15 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
T2515I missense loss of function BRCA2 T2515I lies within the FANCD2-interaction region of the Brca2 protein (UniProt.org). T2515I results in decreased homology-directed DNA repair and is unable to rescue Brca2-null cell survival in culture (PMID: 15695382).
T1346N missense unknown BRCA2 T1346N lies within the POLH-interacting region of the Brca2 protein (UniProt.org). T1346N has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A2851V missense no effect - predicted BRCA2 A2851V lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). A2851V demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
V3081A missense no effect - predicted BRCA2 V3081A lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). V3081A mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
Y3098H missense no effect BRCA2 Y3098H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y3098H mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138).
A1689fs frameshift loss of function - predicted BRCA2 A1689fs results in a change in the amino acid sequence of the Brca2 protein beginning at 1689 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). A1689fs has not been characterized, however, due to the effects of other truncations downstream of A1689 (PMID: 12619154, PMID: 15695382), A1689fs is predicted to lead to a loss of Brca2 protein function.
V159M missense unknown BRCA2 V159M does not lie within any known functional domains of the Brca2 protein (UniProt.org). V159M has been identified in sequencing studies (PMID: 28111427), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
F701C missense unknown BRCA2 F701C lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). F701C has been identified in the scientific literature (PMID: 28591715), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
G3076R missense loss of function - predicted BRCA2 G3076R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G3076R demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
R2502H missense unknown BRCA2 R2502H lies within the FANCD2 and SEM1-interacting regions of the Brca2 protein (UniProt.org). R2502H has been identified in the scientific literature (PMID: 10486320), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A2351G missense unknown BRCA2 A2351G lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). A2351G has been identified in the scientific literature (PMID: 21218378, PMID: 18824701, PMID: 29731985), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
T2681R missense unknown BRCA2 T2681R lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). T2681R has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
D1902N missense unknown BRCA2 D1902N does not lie within any known functional domains of the Brca2 protein (UniProt.org). D1902N has been identified in the scientific literature (PMID: 23415752, PMID: 25916844), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
R2787L missense unknown BRCA2 R2787L lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2787L has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
I2627F missense loss of function BRCA2 I2627F lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). I2627F results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138, PMID: 18451181).
G2584C missense unknown BRCA2 G2584C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2584C has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
R2659T missense loss of function - predicted BRCA2 R2659T lies within the SHFM1/DSS1-interacting region of the Brca2 protein (UniProt.org). R2659T is predicted to lead to a loss of Brca2 protein function due to aberrant splicing and introduction of a premature stop codon (PMID: 18451181).
R2787C missense no effect - predicted BRCA2 R2787C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2787C mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to have no effect on Brca2 protein function.
R2602T missense unknown BRCA2 R2602T lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). R2602T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A3088V missense no effect - predicted BRCA2 A3088V lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). A3088V demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
D1177N missense unknown BRCA2 D1177N does not lie within any known functional domains of the Brca2 protein (UniProt.org). D1177N has been identified in sequencing studies (PMID: 17088437), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
K2316Q missense unknown BRCA2 K2316Q does not lie within any known functional domains of the Brca2 protein (UniProt.org). K2316Q has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
E2847K missense loss of function - predicted BRCA2 E2847K lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). E2847K demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
H2440R missense no effect - predicted BRCA2 H2440R lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). H2440R mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
W2788R missense loss of function - predicted BRCA2 W2788R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). W2788R results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
P2589H missense no effect - predicted BRCA2 P2589H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). P2589H mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
P2352S missense unknown BRCA2 P2352S lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). P2352S has been identified in sequencing studies (PMID: 25583476), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
S3252F missense unknown BRCA2 S3252F does not lie within any known functional domains of the Brca2 protein (UniProt.org). S3252F has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
E2871D missense unknown BRCA2 E2871D does not lie within any known functional domains of the Brca2 protein (UniProt.org). E2871D has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
T1067A missense unknown BRCA2 T1067A does not lie within any known functional domains of the Brca2 protein (UniProt.org). T1067A has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
I1929V missense unknown BRCA2 I1929V does not lie within any known functional domains of the Brca2 protein (UniProt.org). I1929V has been identified in sequencing studies (PMID: 29731985, PMID: 25802882, PMID: 27907908), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
L2106P missense unknown BRCA2 L2106P does not lie within any known functional domains of the Brca2 protein (UniProt.org). L2106P has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
P920S missense unknown BRCA2 P920S lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). P920S has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
T3211K missense unknown BRCA2 T3211K does not lie within any known functional domains of the Brca2 protein (UniProt.org). T3211K has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
E1382del deletion loss of function BRCA2 E1382del results in the deletion of one amino acid in the POLH-interaction region of the Brca2 protein at amino acids 1382 (UniProt.org). E1382del results in decreased homology-directed DNA repair and is unable to rescue Brca2-null cell survival in culture (PMID: 15695382).
R2842L missense loss of function - predicted BRCA2 R2842L lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R2842L results in decreased Brca2 activity, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
N987I missense unknown BRCA2 N987I lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). N987I has been identified in the scientific literature (PMID: 22034289, PMID: 15744044), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Apr 2018).
N991D missense no effect - predicted BRCA2 N991D lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). N991D demonstrates cell viability by rescuing Brca1-deficient embryonic stem cells in culture (PMID: 18607349), and therefore, is predicted to have no effect on Brca2 protein function.
I1349T missense unknown BRCA2 I1349T lies within the POLH-interacting region of the Brca2 protein (UniProt.org). I1349T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
Y3092C missense no effect BRCA2 Y3092C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y3092C mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138).
Q2925R missense loss of function - predicted BRCA2 Q2925R lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Q2925R partially reduces the homology-directed DNA repair function of Brca2 in cultured cells (PMID: 29394989) and therefore, is predicted to result in a loss of Brca2 protein function.
L2686P missense loss of function - predicted BRCA2 L2686P lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). L2686P results in decreased homology-directed DNA repair activity in culture (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
N588D missense unknown BRCA2 N588D does not lie within any known functional domains of the Brca2 protein (UniProt.org). N588D has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
R3052W missense loss of function BRCA2 R3052W lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). R3052W results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and failed to rescue Brca2-deficient embryonic stem cells in culture (PMID: 18607349).
Y3092S missense loss of function - predicted BRCA2 Y3092S lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). Y3092S results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
P2800S missense loss of function - predicted BRCA2 P2800S lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). P2800S results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
F2873C missense no effect - predicted BRCA2 F2873C lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). F2873C demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
G2813E missense no effect - predicted BRCA2 G2813E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2813E mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
L2396F missense unknown BRCA2 L2396F lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). L2396F has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
V1810I missense unknown BRCA2 V1810I does not lie within any known functional domains of the Brca2 protein (UniProt.org). V1810I has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
A1170V missense unknown BRCA2 A1170V does not lie within any known functional domains of the Brca2 protein (UniProt.org). A1170V has been identified in the scientific literature (PMID: 18824701), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
K956T missense unknown BRCA2 K956T lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). K956T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
R2268I missense unknown BRCA2 R2268I does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2268I has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
S3239Y missense unknown BRCA2 S3239Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). S3239Y has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
G3076V missense loss of function - predicted BRCA2 G3076V lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G3076V results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
E462G missense no effect BRCA2 E462G does not lie within any known functional domains of the Brca2 protein (UniProt.org). E462G mediates homology-directed DNA repair and rescues Brca2-null cell survival at levels comparable to wild-type Brca2 in culture (PMID: 15695382).
V2728I missense no effect - predicted BRCA2 V2728I lies within the SEM1-interacting region of the Brca2 protein (UniProt.org). V2728I demonstrates cell viability by rescuing Brca1-deficient embryonic stem cells in culture (PMID: 18607349), and therefore, is predicted to have no effect on Brca2 protein function.
D687H missense unknown BRCA2 D687H lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). D687H has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
P89Q missense unknown BRCA2 P89Q does not lie within any known functional domains of the Brca2 protein (UniProt.org). P89Q has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
N517S missense unknown BRCA2 N517S does not lie within any known functional domains of the Brca2 protein (UniProt.org). N517S has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
R2336H missense loss of function - predicted BRCA2 R2336H does not lie within any known functional domains of the Brca2 protein (UniProt.org). R2336H results in aberrant splicing and introduction of a premature stop codon (PMID: 21719596) and therefore, is predicted to result in a loss of Brca2 protein function.
S2414L missense no effect BRCA2 S2414L lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). S2414L mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
L3011P missense unknown BRCA2 L3011P lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L3011P demonstrates partial effect on homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
S1733F missense unknown BRCA2 S1733F lies within the POLH-interacting region of the Brca2 protein (UniProt.org). S1733F has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
S3396R missense unknown BRCA2 S3396R does not lie within any known functional domains of the Brca2 protein (UniProt.org). S3396R has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
D2965H missense no effect - predicted BRCA2 D2965H lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). D2965H mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 23108138) and therefore, is predicted to have no effect on Brca2 protein function.
H2623R missense loss of function - predicted BRCA2 H2623R lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). H2623R demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
N319T missense no effect - predicted BRCA2 N319T does not lie within any known functional domains of the Brca2 protein (UniProt.org). N319T mediates homology-directed DNA repair to the level comparable with wild type Brca2 in cultured cells (PMID: 18451181) and therefore, is predicted to have no effect on Brca2 protein function.
S196N missense loss of function - predicted BRCA2 S196N does not lie within any known functional domains of the Brca2 protein (UniProt.org). S196N results in aberrant splicing and introduction of a premature stop codon (PMID: 22962691) and therefore, is predicted to result in a loss of Brca2 protein function.
V894I missense unknown BRCA2 V894I lies within the NPM1-interacting region of the Brca2 protein (UniProt.org). V894I has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
K2206N missense unknown BRCA2 K2206N does not lie within any known functional domains of the Brca2 protein (UniProt.org). K2206N has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
L1019V missense no effect - predicted BRCA2 L1019V lies within the BRCA2 repeat 1 of the Brca2 protein (UniProt.org). L1019V mediates homology-directed DNA repair to the level comparable with wild-type Brca2 in cultured cells (PMID: 21671020) and therefore, is predicted to have no effect on Brca2 protein function.
A2351T missense unknown BRCA2 A2351T lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). A2351T has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
S1682G missense unknown BRCA2 S1682G lies within the BRCA2 repeat 5 of the Brca2 protein (UniProt.org). S1682G has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
T3030fs frameshift loss of function - predicted BRCA2 T3030fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 3030 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). T3030fs has not been characterized, however, due to the effects of other truncations downstream of T3030 (PMID: 12619154), T3030fs is predicted to lead to a loss of Brca2 protein function.
C3198R missense unknown BRCA2 C3198R does not lie within any known functional domains of the Brca2 protein (UniProt.org). C3198R has been identified in sequencing studies (PMID: 17924331), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
T3033I missense loss of function - predicted BRCA2 T3033I lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). T3033I results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
R245_D252del deletion unknown BRCA2 R245_D252del results in the deletion of 8 amino acids in the Brca2 protein (UniProt.org). R245_D252del has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
R1190W missense unknown BRCA2 R1190W does not lie within any known functional domains of the Brca2 protein (UniProt.org). R1190W has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
V2466A missense unknown BRCA2 V2466A lies within the FANCD2-interacting region of the Brca2 protein (UniProt.org). V2466A has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
I247Yfs*8 frameshift loss of function - predicted BRCA2 I247Yfs*8 indicates a shift in the reading frame starting at amino acid 247 and terminating 8 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), I247Yfs*8 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
F1182fs frameshift loss of function - predicted BRCA2 F1182fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1182 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). F1182fs has not been characterized, however, due to the effects of other truncations downstream of F1182 (PMID: 12619154, PMID: 15695382), F1182fs is predicted to lead to a loss of Brca2 protein function.
D2606G missense unknown BRCA2 D2606G lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). D2606G demonstrates partial effect on homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
D244Rfs*7 frameshift loss of function - predicted BRCA2 D244Rfs*7 indicates a shift in the reading frame starting at amino acid 244 and terminating 7 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), D244Rfs*7 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
E1441* nonsense loss of function - predicted BRCA2 E1441* results in a premature truncation of the Brca2 protein at amino acid 1441 of 3418 (UniProt.org). E1441* has not been characterized, however, due to the effects of other truncations downstream of E1441 (PMID: 12619154, PMID: 15695382), E1441* is predicted to lead to a loss of Brca2 protein function.
T2766Nfs*11 frameshift loss of function - predicted BRCA2 T2766Nfs*11 indicates a shift in the reading frame starting at amino acid 2766 and terminating 11 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). T2766Nfs*11 has not been characterized, however, due to the effects of other truncations downstream of E2476 (PMID: 12619154), T2766Nfs*11 is predicted to lead to a loss of Brca2 protein function.
D1280V missense unknown BRCA2 D1280V does not lie within any known functional domains of the Brca2 protein (UniProt.org). D1280V has been identified in sequencing studies (PMID: 17924331), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
G2609V missense loss of function - predicted BRCA2 G2609V lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). G2609V demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
V2969M missense unknown BRCA2 V2969M does not lie within any known functional domains of the Brca2 protein (UniProt.org). V2969M has been identified in sequencing studies (PMID: 25948282), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
P375S missense unknown BRCA2 P375S does not lie within any known functional domains of the Brca2 protein (UniProt.org). P375S has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
D2312V missense unknown BRCA2 D2312V does not lie within any known functional domains of the Brca2 protein (UniProt.org). D2312V demonstrates intermediate DNA-repair activity by RECAP assay in a patient sample with mosaic BRCA1 deletion and BRCA2 duplication background (PMID: 30139880), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
S2307L missense unknown BRCA2 S2307L does not lie within any known functional domains of the Brca2 protein (UniProt.org). S2307L has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
D2680G missense no effect - predicted BRCA2 D2680G lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). D2680G demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
N136_L139del deletion unknown BRCA2 N136_L139del results in the deletion of 4 amino acids in the Brca2 protein (UniProt.org). N136_L139del has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown; however, the corresponding cDNA change has been demonstrated to act as a reversion mutation in the context of a specific inactivating BRCA1 mutation, leading to restoration of the BRCA1 open reading frame and wild-type protein function, as demonstrated by interaction with Palb2 and Rad51 similar to wild-type Brca2 levels in culture and association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
T2250A missense unknown BRCA2 T2250A does not lie within any known functional domains of the Brca2 protein (UniProt.org). T2250A has been identified in the scientific literature (PMID: 25843740), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Mar 2018).
P1819S missense unknown BRCA2 P1819S does not lie within any known functional domains of the Brca2 protein (UniProt.org). P1819S has not been characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Feb 2018).
K1574fs frameshift loss of function - predicted BRCA2 K1574fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1574 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). K1574fs has not been characterized, however, due to the effects of other truncations downstream of K1574 (PMID: 12619154, PMID: 15695382), K1574fs is predicted to lead to a loss of Brca2 protein function.
S3123G missense no effect BRCA2 S3123G lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). S3123G mediates homology-directed DNA repair at a level comparable to wild-type Brca2 in cultured cells (PMID: 29394989).
E3342K missense unknown BRCA2 E3342K does not lie within any known functional domains of the Brca2 protein (UniProt.org). E3342K has not been characterized, but is predicted to be deleterious to Brca2 protein function in computational models (PMID: 18724707).
A248Sfs*15 frameshift loss of function - predicted BRCA2 A248Sfs*15 indicates a shift in the reading frame starting at amino acid 248 and terminating 15 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), A248Sfs*15 is predicted to result in a loss of Brca2 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
G2596R missense loss of function - predicted BRCA2 G2596R lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). G2596R demonstrates decreased homology-directed DNA repair in a cell culture assay (PMID: 29394989), and therefore, is predicted to result in a loss of Brca2 protein function.
A75P missense loss of function - predicted BRCA2 A75P does not lie within any known functional domains of the Brca2 protein (UniProt.org). A75P results in reduced interaction with Plk1 in culture (PMID: 24835992) and therefore, is predicted to result in a loss of Brca2 protein function.
L2768H missense no effect - predicted BRCA2 L2768H lies within the DNA-binding domain and SEM1-interacting region of the Brca2 protein (PMID: 12228710, UniProt.org). L2768H demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
V130_N136delinsD indel unknown BRCA2 V130_N136delinsD results in a deletion of seven amino acids in the Brca2 protein combined with the insertion of one new amino acid in the same location (UniProt.org). V130_N136delinsD has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA2 mutation, potentially leading to restoration of the BRCA2 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy and a PARP inhibitor (PMID: 28765325). Y
T1915M missense unknown BRCA2 T1915M lies within the BRC repeats of the Brca2 protein (PMID: 21671020). T1915M has been identified in sequencing studies (PMID: 17341484, PMID: 25589003, PMID: 20104584), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
I1977fs frameshift loss of function - predicted BRCA2 I1977fs results in a change in the amino acid sequence of the Brca2 protein beginning at aa 1977 of 3418, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the nuclear localization sequence (PMID: 10570174), I1977fs is predicted to lead to a loss of Brca2 protein function.
G2812E missense loss of function - predicted BRCA2 G2812E lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). G2812E results in decreased Brca2 function, as indicated by decreased homology-directed DNA repair in cultured cells (PMID: 23108138) and therefore, is predicted to result in a loss of Brca2 protein function.
D2218Y missense unknown BRCA2 D2218Y does not lie within any known functional domains of the Brca2 protein (UniProt.org). D2218Y has been identified in the scientific literature (PMID: 28591715), but has not been biochemically characterized and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
D252Vfs*24 frameshift loss of function - predicted BRCA2 D252Vfs*24 indicates a shift in the reading frame starting at amino acid 252 and terminating 24 residues downstream causing a premature truncation of the 3418 amino acid Brca2 protein (UniProt.org). D252Vfs*24 has not been characterized, however, due to the effects of other truncations downstream of D252 (PMID: 12619154, PMID: 15695382), D252Vfs*24 is predicted to lead to a loss of Brca2 protein function.
E1511G missense unknown BRCA2 E1511G lies within the POLH-interacting region of the Brca2 protein (UniProt.org). E1511G has not been characterized in the scientific literature and therefore, its effect on Brca2 protein function is unknown (PubMed, Nov 2018).
L2929W missense no effect - predicted BRCA2 L2929W lies within the DNA-binding domain of the Brca2 protein (PMID: 12228710). L2929W demonstrates homology-directed DNA repair similar to wild-type Brca2 in a cell culture assay (PMID: 29394989), and therefore, is predicted to have no effect on Brca2 protein function.
Molecular Profile Protein Effect Treatment Approaches
BRCA2 T3349A unknown
BRCA2 P3324L unknown
BRCA2 Q1782fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 Y3035C no effect - predicted
BRCA2 K2498E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2494Q unknown
BRCA2 L2865V no effect
BRCA2 T1414M unknown
BRCA2 N1102Y unknown
BRCA2 K2316R unknown
BRCA2 N1228D unknown
BRCA2 A2786P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S3058G no effect - predicted
BRCA2 L2862P unknown
BRCA2 A2643G no effect - predicted
BRCA2 D2679G no effect - predicted
BRCA2 V2908G no effect
BRCA2 A2951V unknown
BRCA2 S2522F no effect - predicted
BRCA2 Y2726C loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D2611G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R3007G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S3133* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 I2672V no effect - predicted
BRCA2 T256Kfs*19 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D244Efs*10 BRCA2 D244Rfs*7 BRCA2 D252Vfs*24 BRCA2 E260Sfs*15 BRCA2 I247_E254del BRCA2 I247Yfs*8 BRCA2 N255Tfs*21 BRCA2 N257Efs*19 BRCA2 R245_D252del BRCA2 T256Kfs*19
BRCA2 K1565N unknown
BRCA2 K1690N unknown
BRCA2 dec exp MET over exp
BRCA2 dec exp MET dec exp
BRCA2 dec exp no effect
BRCA2 F2562L loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 L929S unknown
BRCA2 N2436I unknown
BRCA2 V1306I unknown
BRCA2 E1382D unknown
BRCA2 S206C unknown
BRCA2 S2509N no effect - predicted
BRCA2 D596H unknown
BRCA2 Q3247H unknown
BRCA2 C1365Y unknown
BRCA2 E919K unknown
BRCA2 L2654P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E537Q unknown
BRCA2 G173C unknown
BRCA2 loss loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 Y1569C unknown
BRCA2 S384F unknown
BRCA2 K1453E unknown
BRCA2 mutant unknown
BRCA2 mut ERBB2 neg
BRCA2 N289H unknown
BRCA2 T582P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D438Y unknown
BRCA2 R2991H no effect - predicted
BRCA2 Y2660D loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 Q2561P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 F2406L no effect
BRCA2 K604* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 Q1037* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2901D no effect
BRCA2 Q2539H unknown
BRCA2 D2723V loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D1420N unknown
BRCA2 D935N unknown
BRCA2 L2647P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E2571G no effect - predicted
BRCA2 A2466V no effect - predicted
BRCA2 L482I unknown
BRCA2 R155I unknown
BRCA2 L2587F no effect - predicted
BRCA2 E456D unknown
BRCA2 L3180F unknown
BRCA2 Q2925H no effect - predicted
BRCA2 C554W loss of function - predicted
BRCA2 P143S unknown
BRCA2 M2676T no effect - predicted
BRCA2 R2973C no effect - predicted
BRCA2 R2418I unknown
BRCA2 G1194D unknown
BRCA2 K3326* no effect
BRCA2 N1747S unknown
BRCA2 V348L unknown
BRCA2 S3332Y unknown
BRCA2 K2729N no effect - predicted
BRCA2 G2596E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 V1643A unknown
BRCA2 Y2997* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 negative unknown
BRCA2 C1265S unknown
BRCA2 L2972W unknown
BRCA2 P168T unknown
BRCA2 F2642S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2793E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R18H unknown
BRCA2 T1785I unknown
BRCA2 A2603P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G1529R unknown
BRCA2 R2659K loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2108H no effect - predicted
BRCA2 L2688P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D2723G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 K2411T no effect - predicted
BRCA2 L2080* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 Q2925K loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 L1904V unknown
BRCA2 S869L unknown
BRCA2 R2502C unknown
BRCA2 P288S unknown
BRCA2 G2837E unknown
BRCA2 T630I unknown
BRCA2 W2725L loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 K607T unknown
BRCA2 N2048I unknown
BRCA2 V3365_S3366insVNYI unknown
BRCA2 R2488T unknown
BRCA2 K513R unknown
BRCA2 E1285fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S2695L no effect
BRCA2 I2821T no effect - predicted
BRCA2 R2488G no effect - predicted
BRCA2 E3002K loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E1879D unknown
BRCA2 N255Tfs*21 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N372H unknown
BRCA2 E3071D no effect - predicted
BRCA2 N272Kfs*2 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R3052Q no effect
BRCA2 T1354A unknown
BRCA2 W2626C loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E2757V no effect - predicted
BRCA2 S2616C unknown
BRCA2 G2584D no effect - predicted
BRCA2 Q2655R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S2704F unknown
BRCA2 D1420Y no effect - predicted
BRCA2 I1607S unknown
BRCA2 W2788S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2063E unknown
BRCA2 K2630Q loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N3124I loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S1424C unknown
BRCA2 P3039L no effect
BRCA2 I1017F unknown
BRCA2 P3063S no effect - predicted
BRCA2 N1642T unknown
BRCA2 D2723A loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 K2950N unknown
BRCA2 Q2858R unknown
BRCA2 L2510P loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2418G unknown
BRCA2 E2020K unknown
BRCA2 D2723H loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D244Efs*10 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 L2653P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 Y3035S no effect - predicted
BRCA2 H1918Y unknown
BRCA2 N257Kfs*17 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D3073G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S3020C no effect - predicted
BRCA2 P2800R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S278N unknown
BRCA2 R2784Q loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 T1887M unknown
BRCA2 A1981S unknown
BRCA2 R2336P unknown
BRCA2 I2944F no effect
BRCA2 R2842H unknown
BRCA2 Y2660C unknown
BRCA2 G3003E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 A2711T unknown
BRCA2 G2508S unknown
BRCA2 R2520Q no effect - predicted
BRCA2 E2476* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 A2233T unknown
BRCA2 I2285V no effect
BRCA2 V1078I unknown
BRCA2 D2679Y no effect - predicted
BRCA2 G3076E loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S2691F loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G602R unknown
BRCA2 S2988G no effect
BRCA2 T1302del loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 L2581W no effect - predicted
BRCA2 N1742I unknown
BRCA2 P365Q unknown
BRCA2 E510* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 P2734H unknown
BRCA2 I605fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2659G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2787H no effect - predicted
BRCA2 Q2384K unknown
BRCA2 S3319Y unknown
BRCA2 A2770T unknown
BRCA2 K2472T unknown
BRCA2 G1771D unknown
BRCA2 R2888C unknown
BRCA2 I2672fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 M784V unknown
BRCA2 V2652M no effect - predicted
BRCA2 K2017T unknown
BRCA2 S2483N unknown
BRCA2 L209F unknown
BRCA2 F1192C unknown
BRCA2 S1172L unknown
BRCA2 I2675V unknown
BRCA2 T868I unknown
BRCA2 E49* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N1784fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N56T unknown
BRCA2 E2663V loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 del loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N257Efs*19 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D806H unknown
BRCA2 S326R unknown
BRCA2 K1691fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E897* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 K1649I unknown
BRCA2 D2665G no effect - predicted
BRCA2 S2243Y unknown
BRCA2 D2913E no effect - predicted
BRCA2 D1352Y unknown
BRCA2 Q1396R unknown
BRCA2 C1200fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D3170G no effect - predicted
BRCA2 G1761V unknown
BRCA2 G2748D loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2585R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 P655R no effect - predicted
BRCA2 Y42C loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S1064* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E2229* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S2807L no effect - predicted
BRCA2 R2784W loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N2113S unknown
BRCA2 A2951T no effect
BRCA2 R2842C loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E3002L loss of function - predicted
BRCA2 H1350N unknown
BRCA2 H1752Y unknown
BRCA2 D479Y unknown
BRCA2 L2792P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 P2639A no effect - predicted
BRCA2 S1982fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2488S no effect - predicted
BRCA2 E2258K unknown
BRCA2 inact mut loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2678G no effect - predicted
BRCA2 Q699H unknown
BRCA2 wild-type no effect
BRCA1 wild-type BRCA2 wild-type
BRCA2 S3016Y unknown
BRCA2 R174C unknown
BRCA2 T3013I no effect - predicted
BRCA2 S2670L unknown
BRCA2 L2721H loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 I247Kfs*2 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S2782N no effect - predicted
BRCA2 S142I unknown
BRCA2 K2849E no effect - predicted
BRCA2 E3002D loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E350* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 I1772S unknown
BRCA2 R2318Q loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E3152K no effect - predicted
BRCA2 L3125H loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 A2632G no effect - predicted
BRCA2 P3194Q unknown
BRCA2 T2722R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 P606L unknown
BRCA2 D191G unknown
BRCA2 R2645fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 H2074N unknown
BRCA2 S1680Y unknown
BRCA2 T1354M unknown
BRCA2 R3384Q unknown
BRCA2 I247_E254del unknown
BRCA2 V211I loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 V3079I unknown
BRCA2 N1878K no effect - predicted
BRCA2 S2216F unknown
BRCA2 N136_L139del BRCA2 N136Ifs*16 BRCA2 V130_N136delinsD
BRCA2 N136Ifs*16 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2845fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S196I unknown
BRCA2 T3195A unknown
BRCA2 G2793R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 K1434I unknown
BRCA2 E2856A no effect - predicted
BRCA2 F1524V unknown
BRCA2 T1673P unknown
BRCA2 A2717S no effect
BRCA2 H1966Y unknown
BRCA2 I332F unknown
BRCA2 K1180R unknown
BRCA2 D3095E loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2609D loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N243Kfs*3 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 V3365fs unknown
BRCA2 G2274V unknown
BRCA2 E260Sfs*15 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 T2515I loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 T1346N unknown
BRCA2 A2851V no effect - predicted
BRCA2 V3081A no effect - predicted
BRCA2 Y3098H no effect
BRCA2 A1689fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 V159M unknown
BRCA2 F701C unknown
BRCA2 G3076R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2502H unknown
BRCA2 A2351G unknown
BRCA2 T2681R unknown
BRCA2 D1902N unknown
BRCA2 R2787L unknown
BRCA2 I2627F loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2584C unknown
BRCA2 R2659T loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2787C no effect - predicted
BRCA2 R2602T unknown
BRCA2 A3088V no effect - predicted
BRCA2 D1177N unknown
BRCA2 K2316Q unknown
BRCA2 E2847K loss of function - predicted
BRCA2 H2440R no effect - predicted
BRCA2 W2788R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 P2589H no effect - predicted
BRCA2 P2352S unknown
BRCA2 S3252F unknown
BRCA2 E2871D unknown
BRCA2 T1067A unknown
BRCA2 I1929V unknown
BRCA2 L2106P unknown
BRCA2 P920S unknown
BRCA2 T3211K unknown
BRCA2 E1382del loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R2842L loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N987I unknown
BRCA2 N991D no effect - predicted
BRCA2 I1349T unknown
BRCA2 Y3092C no effect
BRCA2 Q2925R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 L2686P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N588D unknown
BRCA2 R3052W loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 Y3092S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 P2800S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 F2873C no effect - predicted
BRCA2 G2813E no effect - predicted
BRCA2 L2396F unknown
BRCA2 V1810I unknown
BRCA2 A1170V unknown
BRCA2 K956T unknown
BRCA2 R2268I unknown
BRCA2 S3239Y unknown
BRCA2 G3076V loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E462G no effect
BRCA2 V2728I no effect - predicted
BRCA2 D687H unknown
BRCA2 P89Q unknown
BRCA2 N517S unknown
BRCA2 R2336H loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S2414L no effect
BRCA2 L3011P unknown
BRCA2 S1733F unknown
BRCA2 S3396R unknown
BRCA2 D2965H no effect - predicted
BRCA2 H2623R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 N319T no effect - predicted
BRCA2 S196N loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 V894I unknown
BRCA2 K2206N unknown
BRCA2 L1019V no effect - predicted
BRCA2 A2351T unknown
BRCA2 S1682G unknown
BRCA2 T3030fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 C3198R unknown
BRCA2 T3033I loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 R245_D252del unknown
BRCA2 R1190W unknown
BRCA2 V2466A unknown
BRCA2 I247Yfs*8 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 F1182fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D2606G unknown
BRCA2 D244Rfs*7 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E1441* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 T2766Nfs*11 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D1280V unknown
BRCA2 G2609V loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 V2969M unknown
BRCA2 P375S unknown
BRCA2 D2312V unknown
BRCA2 S2307L unknown
BRCA2 D2680G no effect - predicted
BRCA2 N136_L139del unknown
BRCA2 T2250A unknown
BRCA2 P1819S unknown
BRCA2 K1574fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 S3123G no effect
BRCA2 E3342K unknown
BRCA2 A248Sfs*15 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2596R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 A75P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 L2768H no effect - predicted
BRCA2 V130_N136delinsD unknown
BRCA2 T1915M unknown
BRCA2 I1977fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 G2812E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 D2218Y unknown
BRCA2 D252Vfs*24 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA2 E1511G unknown
BRCA2 L2929W no effect - predicted
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRCA2 D244Efs*10 BRCA2 D244Rfs*7 BRCA2 D252Vfs*24 BRCA2 E260Sfs*15 BRCA2 I247_E254del BRCA2 I247Yfs*8 BRCA2 N255Tfs*21 BRCA2 N257Efs*19 BRCA2 R245_D252del BRCA2 T256Kfs*19 breast cancer predicted - resistant Carboplatin + Olaparib Clinical Study Actionable In a clinical study, a breast cancer patient harboring BRCA2 D252Vfs*24 progressed while being treated with Carboplatin and a PARP inhibitor, and via cell-free DNA testing was found to have acquired nine somatic reversion mutations, BRCA2 D244Efs*10, BRCA2 D244Rfs*7, BRCA2 E260Sfs*15, BRCA2 I247_E254del, BRCA2 I247Yfs*8, BRCA2 N255Tfs*21, BRCA2 N257Efs*19, BRCA2 R245_D252del, BRCA2 T256Kfs*19, which restored the open reading frame, resulting in wild-type BRCA2 protein function (PMID: 28765325). 28765325
BRCA2 dec exp MET over exp triple-receptor negative breast cancer no benefit Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca2 expression via shRNA knockdown did not sensitize triple-receptor negative breast cancer cells with Met overexpression to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
BRCA2 dec exp MET dec exp triple-receptor negative breast cancer sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca2 expression via shRNA knockdown sensitized triple-receptor negative breast cancer cells with low expression of Met to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
BRCA2 dec exp breast cancer sensitive NU1025 Preclinical - Cell culture Actionable In a preclinical study, knockdown of Brca2 with siRNA sensitized breast cancer cell lines to NU1025 in culture (PMID: 15829966). 15829966
BRCA2 loss colorectal cancer sensitive Radiotherapy + YU238259 Preclinical Actionable In a preclinical study, YU238259 and radiotherapy synergistically inhibited survival of colorectal cancer cell lines harboring BRCA2 loss in culture (PMID: 26116172). 26116172
BRCA2 loss ovary adenocarcinoma sensitive YU238259 Preclinical Actionable In a preclinical study, YU238259 demonstrated increased cytotoxicity compared to control in BRCA2-deficient ovarian adenocarcinoma cell lines in culture (PMID: 26116172). 26116172
BRCA2 loss colorectal cancer sensitive Olaparib + YU238259 Preclinical - Cell culture Actionable In a preclinical study, YU238259 and Lynparza (olaparib) synergistically inhibited survival of colorectal cancer cell lines harboring BRCA2 loss in culture (PMID: 26116172). 26116172
BRCA2 loss prostate cancer sensitive Olaparib Phase II Actionable In a Phase II clinical trial, 100% (7/7) of metastatic castration-resistant prostate cancer patients with BRCA2 loss demonstrated response to Lynparza (olaparib) treatment (PMID: 26510020). 26510020
BRCA2 loss colorectal cancer sensitive YU238259 Preclinical - Cell line xenograft Actionable In a preclinical study, YU238259 induced cytotoxicity in a human BRCA2-deficient colorectal cancer cell line in culture and slowed tumor growth in xenograft models (PMID: 26116172). 26116172
BRCA2 loss colorectal adenocarcinoma sensitive AZD6738 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, AZD6738 increased sensitivity to radiotherapy in a colorectal adenocarcinoma cell line deficient for BRCA2 in culture, resulting in a greater decrease in cell survival compared to radiotherapy alone (PMID: 28062704). 28062704
BRCA2 loss colorectal cancer sensitive Etoposide + YU238259 Preclinical Actionable In a preclinical study, YU238259 and Eposin (etoposide) synergistically inhibited survival of colorectal cancer cell lines harboring BRCA2 loss in culture (PMID: 26116172). 26116172
BRCA2 loss ovarian cancer predicted - sensitive APTO-253 Preclinical - Cell culture Actionable In a preclinical study, APTO-253 treatment resulted in decreased viability in BRCA2-deficient ovarian cancer cells in culture (PMID: 29626126). 29626126
BRCA2 loss pancreatic cancer sensitive NMS-P118 + Temozolomide Preclinical - Cell line xenograft Actionable In a preclinical study, NMS-P118 enhanced the effects of Temodar (temozolomide) in BRCA2-deficient pancreatic cancer xenograft models, demonstrating inhibition of tumor growth and a complete response in 50% (3/6) of the models (PMID: 26222319). 26222319
BRCA2 mutant Her2-receptor negative breast cancer sensitive Olaparib FDA approved Actionable In a Phase III trial (OlympiAD) that supported FDA approval, Lynparza (olaparib) treatment resulted in significantly improved median progression-free survival (7.0 vs 4.2 months, HR=0.58, p<0.001) and higher response rate (59.9% vs 28.8%) compared to standard chemotherapy in ERBB2 (HER2)-negative breast cancer patients harboring a germline BRCA mutation (PMID: 28578601; NCT02000622). 28578601
BRCA2 mutant ovarian cancer predicted - sensitive Pamiparib Phase I Actionable In a Phase I trial, BGB-290 treatment resulted in an improved objective response rate in ovarian cancer patients harboring germline BRCA1/2 mutations (58%, 7/12) compared to BRCA1/2 wild-type (25%, 2/8) patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 368PD; NCT02361723). detail...
BRCA2 mutant pancreatic cancer not applicable N/A Guideline Risk Factor Germline BRCA1/2 mutations are associated with increased risk of developing and early onset of pancreatic cancer (NCCN.org). detail...
BRCA2 mutant breast cancer predicted - sensitive Veliparib + Carboplatin Phase I Actionable In a Phase I clinical trial, the combination of Veliparib (ABT-888) and Paraplatin (carboplatin) demonstrated preliminary efficacy in metastatic breast cancer patients, with partial response in 25% (4/16) and stable disease in 62.5% (10/16) of patients with BRCA1/2 mutations or Fanconi Anemia pathway defects (J Clin Oncol 32:5s, 2014 (suppl; abstr 1074)). detail...
BRCA2 mutant ovarian cancer predicted - sensitive Irinotecan + Veliparib Phase I Actionable In a Phase I trial, Veliparib (ABT-888) and Camptosar (irinotecan) combination therapy resulted in partial response in 11% (1/9) and stable disease in 67% (6/9) of ovarian cancer patients harboring germline mutations in BRCA1 or BRCA2 (PMID: 26842236). 26842236
BRCA2 mutant Advanced Solid Tumor predicted - sensitive CX-5461 Phase I Actionable In a Phase I trial, CX-5461 treatment resulted in partial response in a patient with advanced solid tumor harboring BRCA2 mutations, and stable disease in 5 additional patients, 4 of whom harboring BRCA1/2 mutations, and 1 with Li-Fraumeni syndrome (Annals of Oncology, Volume 29, Issue suppl_3, 1 March 2018, abstract 440; NCT02719977). detail...
BRCA2 mutant breast cancer sensitive Olaparib Phase II Actionable In a Phase II clinical trial, Lynparza (olaparib) demonstrated safety and efficacy in breast cancer patients with BRCA2 mutations (PMID: 20609467). 20609467
BRCA2 mutant prostate cancer sensitive Veliparib Phase II Actionable In a Phase II clinical trial, Veliparib (ABT-888) demonstrated preliminary clinical activity in patients with BRCA2-mutant metastatic castration resistant prostate cancer, with an overall response rate of 66% (2/3) and clinical benefit rate of 100% (3/3) (J Clin Oncol 33, 2015 (suppl 7; abstr 170)). detail...
BRCA2 mutant ovarian carcinoma no benefit Bevacizumab + Carboplatin + Paclitaxel Clinical Study Actionable In a clinical study, ovarian carcinoma patients harboring a mutation in either BRCA1, BRCA2, or another homologous recombination repair (HRR) gene did not demonstrate a significant difference in progression free survival when Avastin (bevacizumab) was added to the combined platinum therapy, Platinol (carboplatin) and Taxol (paclitaxel), versus the platinum therapy with placebo, suggesting HRR gene mutations do not impact the effect of Avastin (bevacizumab) (PMID: 29191972). 29191972
BRCA2 mutant Her2-receptor negative breast cancer predicted - sensitive Cisplatin + Veliparib + Vinorelbine Phase I Actionable In a Phase I trial, Veliparib (ABT-888) in combination with Platinol (cisplatin) and Navelbine (vinorelbine) resulted in a greater complete response (7%, 1/14), partial response (50%, 7/14), and 6-month progression free survival rate (71%, 10/14) in Erbb2 (Her2) negative breast cancer patients harboring germline BRCA1 or BRCA2 mutations compared to BRCA wild-type patients (PMID: 26801247). 26801247
BRCA2 mutant ovarian cancer sensitive Olaparib FDA approved Actionable In a Phase II trial that supported FDA approval, treatment with Lynparza (olaparib) resulted in a tumor response rate of 34% (n=137) and median duration of response of 7.9 months in ovarian cancer patients harboring germline BRCA1/2 mutations that had received 3 or more lines of chemotherapy (PMID: 26187614, PMID: 25366685; NCT01078662). 26187614 25366685
BRCA2 mutant ovarian cancer sensitive Olaparib Guideline Actionable Lynparza (olaparib) is included in the guidelines as recurrence therapy for ovarian cancer patients harboring BRCA1/2 germline mutations (NCCN.org). detail...
BRCA2 mutant ovarian cancer sensitive Olaparib Preclinical - Pdx Actionable In a preclinical study, Lynparza (olaparib) decreased tumor growth in patient-derived xenografts carrying BRCA2 mutation (PMID: 21097693). 21097693
BRCA2 mutant ovarian cancer sensitive Olaparib Phase III Actionable In a Phase III trial, ovarian cancer patients who are platinum-sensitive and relapsed and harbor either mutant BRCA1 or mutant BRCA2 demonstrated a greater progression-free survival (19.1 mo vs 5.5 mo) when treated with Lynparza (olaparib) tablets as maintenance therapy compared to placebo (PMID: 28754483; NCT01874353). 28754483
BRCA2 mutant pancreatic cancer predicted - sensitive Rucaparib Phase II Actionable In a Phase II trial, Rubraca (rucaparib) treatment resulted in an objective response rate of 11% (2/19) and a disease control rate of 32% (6/19) in advanced pancreatic cancer patients with a known deleterious BRCA mutation, of whom 79% harbored a BRCA2 mutation (J Clin Oncol 34, 2016 (suppl; abstr 4110)). detail...
BRCA2 mutant ovarian cancer predicted - sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment in ovarian cancer patients harboring germline deleterious BRCA1/2 mutations resulted in an objective response rate of 48%, including one complete response, and a clinical benefit rate of 76% at 24 weeks (PMID: 28242752). 28242752
BRCA2 mutant triple-receptor negative breast cancer decreased response Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment in patients with triple-receptor negative breast cancer carrying a BRCA1 and/or BRCA2 mutation resulted in a lower clinical benefit rate (56% vs 89%) compared to treatment in non-triple-receptor negative breast cancer patients carrying a BRCA1/2 mutation (PMID: 28242752). 28242752
BRCA2 mutant breast cancer predicted - sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN673) treatment in breast cancer patients harboring germline deleterious BRCA1/2 mutations resulted in an objective response rate of 50% (7/14), including one patient with a complete response and six patients with a partial response, and resulted in a median progression free survival of 34.6 weeks (PMID: 28242752). 28242752
BRCA2 mutant pancreatic cancer sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment in pancreatic cancer patients resulted in four patients with a clinical benefit including a partial response in one patient harboring a BRCA2 mutation (PMID: 28242752). 28242752
BRCA2 mutant ovarian cancer predicted - sensitive Niraparib Phase III Actionable In a Phase III trial (NOVA), maintenance Zejula (niraparib) therapy significantly improved median progression-free survival compared to placebo (21.0 vs. 5.5 months, HR=0.27) in patients with platinum-sensitive, recurrent ovarian cancer harboring germline BRCA mutations (PMID: 27717299; NCT01847274). 27717299
BRCA2 mutant ovarian cancer sensitive Rucaparib Guideline Actionable Rubraca (rucaparib) is included in the guidelines as recurrence therapy for ovarian cancer patients harboring BRCA1/2 germline mutations (NCCN.org). detail...
BRCA2 mutant ovarian cancer sensitive Rucaparib Phase II Actionable In a Phase II clinical trial, treatment with Rubraca (rucaparib) was tolerated and demonstrated activity in ovarian cancer patients with germline BRCA1/2 mutations (PMID: 27002934). 27002934
BRCA2 mutant ovarian cancer sensitive Rucaparib Phase III Actionable In a Phase III trial (ARIEL3), Rubraca (rucaparib) treatment resulted in significantly improved progression-free survival compared to placebo (16.6 vs 5.4 months, HR=0.23, p=0.0001) in patients with BRCA-mutant, platinum-sensitive ovarian cancer (PMID: 28916367; NCT01968213). 28916367
BRCA2 mutant ovarian cancer sensitive Rucaparib FDA approved Actionable In a retrospective analysis of two Phase II trials (ARIEL 2 and Study 10) that supported FDA approval, Rubraca (rucaparib) treatment resulted in an objective response rate of 54% (21/39) in high-grade ovarian cancer patients harboring BRCA2 mutations (PMID: 28751443). 28751443
BRCA2 mutant Advanced Solid Tumor predicted - sensitive ABT-767 Phase I Actionable In a Phase I trial, ABT-767 treatment resulted in a response rate of 18% (n=14/79) in patients with high grade serous ovarian cancer, fallopian tube, or primary peritoneal cancer or with solid tumors harboring germline BRCA1 or BRCA2 mutations, with an overall 6 month time to progression rate of 22% (Ann Oncol (2014) 25 (suppl 4): iv150). detail...
BRCA2 negative Advanced Solid Tumor sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, BRCA2-deficient cancer cell lines with DNA repair deficiency demonstrated high sensitivity to the PARP inhibitor, Talazoparib (BMN-673) (PMID: 23881923). 23881923
BRCA2 del colorectal adenocarcinoma sensitive PR-104 Preclinical - Cell line xenograft Actionable In a preclinical study, colorectal adenocarcinoma cells with BRCA2 deletion demonstrated increased sensitivity to PR-104 compared to cells with intact BRCA2 in culture and in cell line xenograft models (PMID: 25193512) 25193512
BRCA2 del colorectal adenocarcinoma sensitive Evofosfamide Preclinical - Cell line xenograft Actionable In a preclinical study, colorectal adenocarcinoma cells with BRCA2 deletion demonstrated increased sensitivity to Evofosfamide (TH-302) compared to cells with intact BRCA2 in culture and human cell line xenograft models (PMID: 25193512). 25193512
BRCA2 del colorectal adenocarcinoma sensitive Chlorambucil Preclinical Actionable In a preclinical study, colorectal adenocarcinoma cells with BRCA2 deletion demonstrated increased sensitivity to Ambochlorin (chlorambucil) compared to cells with intact BRCA2 in culture (PMID: 25193512). 25193512
BRCA2 del colorectal adenocarcinoma sensitive Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, Platinol (cisplatin) inhibited growth of a human colorectal adenocarcinoma cell line harboring BRCA2 deletion in culture, and inhibited tumor growth in xenograft models (PMID: 25193512). 25193512
BRCA2 inact mut ovarian cancer no benefit Veliparib + Cyclophosphamide Phase II Actionable In a Phase II clinical trial, the combination of Veliparib (ABT-888) and Cytoxan (cyclophosphamide) did not demonstrate improved response rate or progression-free survival over Cytoxan (cyclophosphamide) alone in ovarian cancer patients harboring deleterious mutations in BRCA1 or BRCA2 (PMID: 25589624). 25589624
BRCA2 inact mut Advanced Solid Tumor predicted - sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring deleterious BRCA1/2 mutations (J Clin Oncol 31, 2013 (suppl; abstr 2580)). detail...
BRCA2 inact mut breast cancer sensitive AZD2461 Preclinical - Cell culture Actionable In a preclinical study, a BRCA2-deficient breast cancer cell line resistant to Lynparza (olaparib) demonstrated sensitivity to treatment with AZD2461 in culture, resulting in reduced cell viability (PMID: 27550455). 27550455
BRCA2 inact mut breast cancer predicted - sensitive Carboplatin + Paclitaxel + Veliparib Phase II Actionable In a Phase II trial, the combination of Veliparib (ABT-888), Paraplatin (carboplatin), and Taxol (paclitaxel) resulted in a higher objective response rate (77.8% vs 61.3%) compared to placebo plus Paraplatin (carboplatin) and Taxol (paclitaxel) in breast cancer patients harboring either BRCA1 or BRCA2 deleterious mutations (SABCS, 2016, Abstract # S2-05). detail...
BRCA2 inact mut prostate cancer predicted - sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring deleterious BRCA1/2 mutations, including one patient with prostate cancer (J Clin Oncol 31, 2013 (suppl; abstr 2580)). detail...
BRCA2 inact mut Her2-receptor negative breast cancer sensitive Talazoparib FDA approved Actionable In a Phase III trial (EMBRACA) that supported FDA approval, Talzenna (talazoparib) treatment resulted in significantly longer median progression-free survival (8.6 vs 5.6 months, HR=0.54, p<0.001), and higher objective response rate (62.6% vs 27.2%, OR=5.0, p<0.001) compared to standard chemotherapy in patients with advanced ERBB2 (HER2)-negative breast cancer harboring known deleterious or suspected deleterious germline mutations in BRCA1 or BRCA2 (PMID: 30110579; NCT01945775). 30110579
BRCA2 inact mut breast cancer sensitive Olaparib Phase II Actionable In a Phase II clinical trial, Lynparza (olaparib) demonstrated safety and efficacy in breast cancer patients with BRCA2 inactivating mutations (PMID: 20609467). 20609467
BRCA2 inact mut Advanced Solid Tumor sensitive E7449 Preclinical Actionable In a preclinical study, E7449 inhibited proliferation of a BRCA2-deficient cell line in culture, which demonstrated increased sensitivity compared to cells without DNA repair mutations (PMID: 26513298). 26513298
BRCA2 wild-type colorectal adenocarcinoma sensitive AZD6738 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, AZD6738 increased sensitivity to radiotherapy in a colorectal adenocarcinoma cell line harboring wild-type BRCA2 in culture, resulting in a greater decrease in cell survival compared to radiotherapy alone (PMID: 28062704). 28062704
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive KU-0063794 + Talazoparib Preclinical Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Talazoparib (BMN673) when treatment was combined with KU-0063794, resulting in greater decreased cell proliferation and apoptosis in culture (PMID: 26546619). 26546619
BRCA1 wild-type BRCA2 wild-type ovarian serous carcinoma predicted - sensitive Prexasertib Phase II Actionable In a Phase II trial, Prexasertib (LY2606368) treatment resulted in a partial response in 33% (8/24) of BRCA wild-type patients with high-grade serous ovarian cancer (PMID: 29361470; NCT02203513). 29361470
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer predicted - sensitive Cisplatin + VX-970 Phase I Actionable In a Phase I trial, VX-970 in combination with Platinol (cisplatin) resulted in an objective response rate of 38.9% (7/18, all partial responses) and a disease control rate of 72.2% (13/18) in patients with BRCA1/2 wild-type triple-receptor negative breast cancer (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 242PD; NCT02157792). detail...
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive Everolimus + Talazoparib Preclinical - Cell line xenograft Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Talazoparib (BMN-673) when treatment was combined with Afinitor (everolimus), resulting in greater decreased cell proliferation and apoptosis in culture and reduced tumor volume in xenograft models (PMID: 26546619). 26546619
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive Olaparib + KU-0063794 Preclinical Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Lynparza (olaparib) when treatment was combined with KU-0063794, resulting in greater decreased cell proliferation and apoptosis in culture (PMID: 26546619). 26546619
BRCA1 wild-type BRCA2 wild-type ovarian cancer predicted - sensitive Niraparib Phase III Actionable In a Phase III trial (NOVA), Zejula (niraparib) maintenance therapy improved median progression-free survival compared to placebo (9.3 vs. 3.9 months, HR=0.45) in platinum-sensitive, recurrent ovarian cancer patients without germline BRCA mutations, with and without homologous recombination deficiency (12.9 vs. 3.8 months, HR=0.38) (PMID: 27717299; NCT01847274). 27717299
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive Olaparib + Everolimus Preclinical Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Lynparza (olaparib) when treatment was combined with Afinitor (everolimus), resulting in greater decreased cell proliferation and apoptosis in culture (PMID: 26546619). 26546619
BRCA2 N136_L139del BRCA2 N136Ifs*16 BRCA2 V130_N136delinsD breast cancer resistant Talazoparib Clinical Study Actionable In a clinical study, a patient with breast cancer harboring the germline mutation, BRCA2 N136Ifs*16, acquired two BRCA2 reversion mutations, V130_N136delinsD and N136_L139del, as detected in cell-free DNA post treatment with Paraplatin (carboplatin), and subsequently, did not respond to treatment with Talazoparib (BMN-673) (PMID: 28765325). 28765325