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| Gene Symbol | PALB2 | ||||||||||
| Synonyms | BROVCA5 | FANCN | PNCA3 | ||||||||||
| Gene Description | PALB2, partner and localizer of BRCA2, recruits Brca2 and Rad51 to repair DNA through homologous recombination (PMID: 24998779, PMID: 30638972). PALB2 loss of function mutations have been linked to hereditary breast cancer (PMID: 25135369) and male breast cancer (PMID: 31067289). | ||||||||||
| ACMG Incidental List v3.0: |
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| Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
|---|---|---|---|---|
| A1017T | missense | no effect - predicted | PALB2 A1017T lies within WD repeat 4 of the Palb2 protein (UniProt.org). A1017T results in BRCA2 binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| A1025R | missense | loss of function | PALB2 A1025R lies within WD repeat 4 of the Palb2 protein (UniProt.org). A1025R confers a loss of function to Palb2 as demonstrated by a loss of binding to Brca2 in an in vitro assay (PMID: 19609323), and decreased homology-directed DNA repair activity in a reporter assay (PMID: 33964450). | |
| A1025T | missense | no effect | PALB2 A1025T lies within WD repeat 4 of the palb2 protein (UniProt.org). A1025T results in homologous repair activity similar to wild-type Palb2 in culture (PMID: 31636395, PMID: 33964450), BRCA2-binding similar to wild-type in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400). | |
| A1079S | missense | unknown | PALB2 A1079S lies within WD repeat 5 of the Palb2 protein (UniProt.org). A1079S results in increased sensitivity to DNA damage in patient cells (PMID: 34382369), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| A1173S | missense | unknown | PALB2 A1173S lies within WD repeat 7 of the Palb2 protein (UniProt.org). A1173S has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| A291V | missense | unknown | PALB2 A291V lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). A291V has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Mar 2024). | |
| A308T | missense | unknown | PALB2 A308T lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). A308T has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Mar 2024). | |
| A38G | missense | unknown | PALB2 A38G lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). A38G demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| A38V | missense | unknown | PALB2 A38V lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). A38V demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| A712P | missense | no effect - predicted | PALB2 A712P does not lie within any known functional domains of the Palb2 protein (UniProt.org). A712P results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| A712V | missense | no effect - predicted | PALB2 A712V does not lie within any known functional domains of the Palb2 protein (UniProt.org). A712V results in homology-directed DNA repair similar to wild-type Palb2 in a reporter assay (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| A915T | missense | unknown | PALB2 A915T lies within WD repeat 1 of the Palb2 protein (UniProt.org). A915T has not been characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Mar 2024). | |
| A968G | missense | unknown | PALB2 A968G lies within WD repeat 3 of the Palb2 protein (UniProt.org). A968G has been identified in sequencing studies (PMID: 32659497, PMID: 34359559), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Dec 2023). | |
| amp | none | no effect | PALB2 amplification indicates an increased number of copies of the PALB2 gene. However, the mechanism causing the increase is unspecified. | |
| C1060S | missense | unknown | PALB2 C1060S lies within WD repeat 5 of the Palb2 protein (UniProt.org). C1060S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| C419G | missense | unknown | PALB2 C419G lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). C419G results in chromatin binding similar to wild-type Palb2 in cultured cells (PMID: 29387807), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| C419P | missense | unknown | PALB2 C419P lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). C419P results in chromatin binding similar to wild-type Palb2 in cultured cells (PMID: 29387807), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| C419R | missense | unknown | PALB2 C419R lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). C419R demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| C77Vfs*100 | frameshift | loss of function - predicted | PALB2 C77Vfs*100 indicates a shift in the reading frame starting at amino acid 77 and terminating 100 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). C77Vfs*100 results in indeterminate homology-directed DNA repair in cultured cells (PMID: 33964450), and due to the effects of other truncation mutations downstream of C77 (PMID: 33964450, PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| C882fs | frameshift | loss of function - predicted | PALB2 C882fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 882 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). C882fs results in impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| D1122N | missense | unknown | PALB2 D1122N lies within WD repeat 6 of the Palb2 protein (UniProt.org). D1122N has not been characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| D1156H | missense | unknown | PALB2 D1156H lies within WD repeat 7 of the Palb2 protein (UniProt.org). D1156H has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| D134N | missense | no effect - predicted | PALB2 D134N lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). D134N results in levels of homologous recombination (PMID: 33169439) and DNA damage-induced cell cycle checkpoint maintenance similar to wild-type protein, does not demonstrate reduced homology-directed DNA repair activity in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| D219G | missense | unknown | PALB2 D219G lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). D219G has been identified in sequencing studies (PMID: 23935836, PMID: 20122277, PMID: 26283626), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| D498Y | missense | unknown | PALB2 D498Y lies within the DNA-binding region of the Palb2 protein (UniProt.org). D498Y does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| D584E | missense | unknown | PALB2 D584E does not lie within any known functional domains of the Palb2 protein (UniProt.org). D584E has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| D595A | missense | unknown | PALB2 D595A does not lie within any known functional domains of the Palb2 protein (UniProt.org). D595A has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| D595Mfs*4 | frameshift | loss of function - predicted | PALB2 D595Mfs*4 indicates a shift in the reading frame starting at amino acid 595 and terminating four residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). D595Mfs*4 has not been characterized, however, due to the effects of other truncation mutations downstream of D595 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| D616H | missense | unknown | PALB2 D616H does not lie within any known functional domains of the Palb2 protein (UniProt.org). D616H does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| D777N | missense | unknown | PALB2 D777N lies within a region of the Palb2 protein required for POLH interaction and POLH DNA synthesis stimulation (UniProt.org). D777N has been identified in sequencing studies (PMID: 31822803, PMID: 30309218, PMID: 24293293), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Dec 2023). | |
| D803N | missense | unknown | PALB2 D803N lies within a region of the Palb2 protein required for POLH interaction and POLH DNA synthesis stimulation (UniProt.org). D803N has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| D871G | missense | no effect - predicted | PALB2 D871G lies within WD repeat 1 of the Palb2 protein (UniProt.org). D871G results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| D893E | missense | unknown | PALB2 D893E lies within WD repeat 1 of the Palb2 protein (UniProt.org). D893E has been identified in sequencing studies (PMID: 22842228), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| D927A | missense | unknown | PALB2 D927A lies within WD repeat 2 of the Palb2 protein (UniProt.org). D927A does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| D986Y | missense | unknown | PALB2 D986Y lies within WD repeat 3 of the Palb2 protein (UniProt.org). D986Y has not been characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| dec exp | none | no effect | PALB2 dec exp indicates decreased expression of the Palb2 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified. | |
| del | deletion | loss of function | PALB2 del indicates a deletion of the PALB2 gene. | |
| del exon11 | deletion | unknown | PALB2 del exon11 indicates a deletion of exon 11 of the PALB2 gene. | |
| E1010* | nonsense | loss of function - predicted | PALB2 E1010* results in a premature truncation of the Palb2 protein at amino acid 1010 of 1186 (UniProt.org). E1010* has not been characterized however, due to the effects of other truncation mutations downstream of E1010 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| E1018D | missense | no effect - predicted | PALB2 E1018D lies within WD repeat 4 of the Palb2 protein (UniProt.org). E1018D results in DNA damage-induced cell cycle checkpoint maintenance and homology-directed DNA repair activity similar to wild-type in cultured cells (PMID: 31757951, PMID: 35853885), and therefore, is predicted to have no effect on Palb2 protein function. | |
| E1083D | missense | unknown | PALB2 E1083D lies within WD repeat 5 of the Palb2 protein (UniProt.org). E1083D does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| E181* | nonsense | loss of function - predicted | PALB2 E181* results in a premature truncation of the Palb2 protein at amino acid 181 of 1186 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), E181* is predicted to lead to a loss of Palb2 protein function. | |
| E19D | missense | unknown | PALB2 E19D lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). E19D has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| E230* | nonsense | loss of function - predicted | PALB2 E230* results in a premature truncation of the Palb2 protein at amino acid 230 of 1186 (UniProt.org). E230* results in impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| E3* | nonsense | loss of function - predicted | PALB2 E3* results in a premature truncation of the Palb2 protein at amino acid 3 of 1186 (UniProt.org). E3* has not been characterized however, due to the effects of other truncation mutations downstream of E3 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| E331Q | missense | no effect - predicted | PALB2 E331Q lies within the DNA-binding region of the Palb2 protein (UniProt.org). E331Q results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| E347K | missense | unknown | PALB2 E347K lies within the DNA-binding region of the Palb2 protein (UniProt.org). E347K has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| E352Q | missense | unknown | PALB2 E352Q lies within the DNA-binding region of the Palb2 protein (UniProt.org). E352Q has been identified in the scientific literature (PMID: 23977390, PMID: 30171174, PMID: 35087742), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| E373G | missense | unknown | PALB2 E373G lies within the DNA-binding region of the Palb2 protein (UniProt.org). E373G has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| E407* | nonsense | loss of function - predicted | PALB2 E407* results in a premature truncation of the Palb2 protein at amino acid 407 of 1186 (UniProt.org). E407* has not been characterized, however, due to the effects of other truncation mutations downstream of E407 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| E426A | missense | unknown | PALB2 E426A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). E426A retains chromatin binding in an in vitro assay (PMID: 32041954), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| E42K | missense | no effect - predicted | PALB2 E42K lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). E42K results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| E53K | missense | unknown | PALB2 E53K lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). E53K has been identified in sequencing studies (PMID: 33193564), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Dec 2023). | |
| E645K | missense | unknown | PALB2 E645K does not lie within any known functional domains of the Palb2 protein (UniProt.org). E645K has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Mar 2024). | |
| E669fs | frameshift | loss of function - predicted | PALB2 E669fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 669 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). E669fs results in protein expression similar to wild-type Palb2, however, demonstrates impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| E672Q | missense | no effect | PALB2 E672Q does not lie within any known functional domains of the Palb2 protein (UniProt.org). E672Q results in homology-directed DNA repair activity similar to wild-type Palb2 in a reporter assay (PMID: 33964450), and homology-directed DNA repair activity similar to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951). | |
| E837* | nonsense | loss of function - predicted | PALB2 E837* results in a premature truncation of the Palb2 protein at amino acid 837 of 1186 (UniProt.org). E837* results in impaired homologous recombination in cultured cells (PMID: 33169439), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| E837K | missense | unknown | PALB2 E837K lies within a region of the Palb2 protein required for POLH interaction and POLH DNA synthesis stimulation (UniProt.org). E837K has been identified in sequencing studies (PMID: 30702443, PMID: 24755471, PMID: 29190888), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| E892K | missense | unknown | PALB2 E892K lies within WD repeat 1 of the Palb2 protein (UniProt.org). E892K has been identified in sequencing studies (PMID: 25356972, PMID: 25575445), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| E940G | missense | unknown | PALB2 E940G lies within WD repeat 2 of the Palb2 protein (UniProt.org). E940G does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| E94K | missense | no effect - predicted | PALB2 E94K lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). E94K results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| F1181Lfs*54 | frameshift | loss of function - predicted | PALB2 F1181Lfs*54 indicates a shift in the reading frame starting at amino acid 1181 and terminating 54 residues downstream, resulting in a premature truncation of the functional protein and extension of the 1186 amino acid Palb2 protein length by 49 amino acids (UniProt.org). F1181Lfs*54 has not been characterized, however, due to the effects of other truncation mutations downstream of F1181 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| F404L | missense | no effect - predicted | PALB2 F404L lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). F404L results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| F440fs | frameshift | loss of function - predicted | PALB2 F440fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 440 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). F440fs has not been characterized however, due to the effects of other truncation mutations downstream of F440 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| G1043A | missense | loss of function - predicted | PALB2 G1043A lies within WD repeat 4 of the Palb2 protein (UniProt.org). G1043A does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), however, results in decreased Brca2 binding, reduced Palb2 recruitment to DNA damage sites, and impaired homology-directed DNA repair activity in cultured cells in another study (PMID: 31586400), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| G1043D | missense | loss of function | PALB2 G1043D lies within WD repeat 4 of the Palb2 protein (UniProt.org). G1043D confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability, reduced Rad51 foci formation, and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31757951). | |
| G1043V | missense | loss of function | PALB2 G1043V lies within WD repeat 4 of the Palb2 protein (UniProt.org). G1043V results in decreased Palb2 protein stability, loss of nuclear localization, impaired homology-directed DNA repair activity in cultured cells, and confers sensitivity to PARP inhibition in PALB2-deficient cells (PMID: 33811135). | |
| G1135E | missense | unknown | PALB2 G1135E lies within WD repeat 6 of the Palb2 protein (UniProt.org). G1135E does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| G115V | missense | no effect - predicted | PALB2 G115V lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). G115V results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| G1174R | missense | unknown | PALB2 G1174R lies within WD repeat 7 of the Palb2 protein (UniProt.org). G1174R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| G401R | missense | unknown | PALB2 G401R lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). G401R demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| G439V | missense | unknown | PALB2 G439V lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). G439V has been identified in sequencing studies (PMID: 26580448), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| G808* | nonsense | loss of function - predicted | PALB2 G808* results in a premature truncation of the Palb2 protein at amino acid 808 of 1186 (UniProt.org). G808* has not been characterized however, due to the effects of other truncation mutations downstream of G808 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| G866V | missense | unknown | PALB2 G866V lies within WD repeat 1 of the Palb2 protein (UniProt.org). G866V does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| G937R | missense | loss of function | PALB2 G937R lies within WD repeat 2 of the Palb2 protein (UniProt.org). G937R confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability, reduced Rad51 foci formation, and impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31757951). | |
| G964V | missense | unknown | PALB2 G964V lies within WD repeat 3 of the Palb2 protein (UniProt.org). G964V has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| G971R | missense | unknown | PALB2 G971R lies within WD repeat 3 of the Palb2 protein (UniProt.org). G971R has not been characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| G998E | missense | no effect | PALB2 G998E lies within WD repeat 3 of the Palb2 protein (UniProt.org). G998E results in Brca2 binding, Rad51 foci formation, and DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31586400, PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 31757951). | |
| H1076D | missense | unknown | PALB2 H1076D lies within WD repeat 5 of the Palb2 protein (UniProt.org). H1076D has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| H1184L | missense | unknown | PALB2 H1184L lies within WD repeat 7 of the Palb2 protein (UniProt.org). H1184L demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| H46Y | missense | loss of function - predicted | PALB2 H46Y lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). H46Y results in subcellular localization, RAD51 foci formation, and homologous repair activity similar to wild-type Palb2 in cultured cells and BRCA1 binding similar to wild-type protein in a mammalian two-hybrid assay, but fails to rescue PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| I1037T | missense | unknown | PALB2 I1037T lies within WD repeat 4 of the Palb2 protein (UniProt.org). The functional effect of I1037T is conflicting as it results in decreased protein stability and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but demonstrates homology-directed DNA repair activity similar to wild-type Palb2 in a reporter assay in another study (PMID: 33964450). | |
| I1051S | missense | unknown | PALB2 I1051S lies within WD repeat 4 of the Palb2 protein (UniProt.org). I1051S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| I1093T | missense | no effect | PALB2 I1093T lies within WD repeat 5 of the palb2 protein (UniProt.org). I1093T results in homologous repair activity similar to wild-type protein in culture (PMID: 31636395), demonstrates subcellular localization and recruitment to dsDNA damage sites comparable to wild-type Palb2 in culture, results in BRCA2 binding similar to wild-type protein in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400). | |
| I1180T | missense | no effect - predicted | PALB2 I1180T lies within WD repeat 7 of the Palb2 protein (UniProt.org). I1180T results in Brca2 binding similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| I309V | missense | no effect | PALB2 I309V lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). I309V demonstrates homology-directed DNA repair activity similar to wild-type Palb2 in an in vitro assay (PMID: 33964450) and in cultured cells lacking Tp53 (PMID: 31636395). | |
| I676T | missense | no effect - predicted | PALB2 I676T does not lie within any known functional domains of the Palb2 protein (UniProt.org). I676T results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| I76V | missense | no effect - predicted | PALB2 I76V lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). I76V results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| I887V | missense | unknown | PALB2 I887V lies within WD repeat 1 of the Palb2 protein (UniProt.org). I887V has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| I944N | missense | loss of function | PALB2 I944N lies within WD repeat 2 of the Palb2 protein (UniProt.org). I944N confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability (PMID: 31757951), reduced Brca2 and Rad51 binding, recruitment to DNA damage sites, and Rad51 foci formation, aberrant cytosolic accumulation (PMID: 31636395), and loss of homology-directed DNA repair activity in cultured cells (PMID: 31636395, PMID: 31757951). | |
| I966T | missense | unknown | PALB2 I966T lies within WD repeat 3 of the Palb2 protein (UniProt.org). I966T does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| I966V | missense | no effect - predicted | PALB2 I966V lies within WD repeat 3 of the Palb2 protein (UniProt.org). I966V results in BRCA2 binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| inact mut | unknown | loss of function | PALB2 inact mut indicates that this variant results in a loss of function of the Palb2 protein. However, the specific amino acid change has not been identified. | |
| K1041T | missense | no effect - predicted | PALB2 K1041T lies within WD repeat 4 of the Palb2 protein (UniProt.org). K1041T results in BRCA2 binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| K1048Rfs*27 | frameshift | loss of function - predicted | PALB2 K1048Rfs*27 indicates a shift in the reading frame starting at amino acid 1048 and terminating 27 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K1048Rfs*27 has not been characterized however, due to the effects of other truncation mutations downstream of K1048 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| K1098* | nonsense | loss of function | PALB2 K1098* results in a premature truncation of the Palb2 protein at amino acid 1098 of 1186 (UniProt.org). K1098* confers a loss of function to Palb2 protein as indicated by a loss of binding to Brca2, Rad51c, and Rad51 (PMID: 24141787), reduced Brca2 and Rad51 foci formation, and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 19584259). | |
| K142Nfs*35 | frameshift | loss of function - predicted | PALB2 K142Nfs*35 indicates a shift in the reading frame starting at amino acid 142 and terminating 35 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K142Nfs*35 has not been characterized however, due to the effects of other truncation mutations downstream of K142 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| K16M | missense | unknown | PALB2 K16M lies within the DNA-binding, BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). K16M results in decreased Brca1 interaction, homology-directed DNA repair activity, and Palb2 and Rad51 foci formation in cultured cells, but maintains Rad51 binding, IR-induced G2/M checkpoint response, and rescues sensitivity to DNA-damaging agents to similar levels of wild-type protein in culture (PMID: 35853885), and therefore, its effect on Palb2 protein function is unknown. | |
| K18R | missense | unknown | PALB2 K18R lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). K18R demonstrates subcellular localization, BRCA1 binding, recruitment to DNA damage sites, and RAD51 foci formation similar to wild-type Palb2 (PMID: 31586400, PMID: 28319063), and retains homologous repair activity in culture (PMID: 31586400, PMID: 33964450), but results in decreased homologous repair activity in culture in another study (PMID: 28319063), and fails to rescue PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, its effect on Palb2 protein function is unknown. | |
| K25* | nonsense | loss of function - predicted | PALB2 K25* results in a premature truncation of the Palb2 protein at amino acid 25 of 1186 (UniProt.org). K25* has not been characterized however, due to the effects of other truncation mutations downstream of K25 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| K30N | missense | no effect | PALB2 K30N lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). K30N results in homology-directed DNA repair (PMID: 28319063, PMID: 31586400, PMID: 33964450) and BRCA1 binding similar to wild-type Palb2, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 28319063, PMID: 31586400). | |
| K346Tfs*13 | frameshift | loss of function - predicted | PALB2 K346Tfs*13 indicates a shift in the reading frame starting at amino acid 346 and terminating 13 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K346Tfs*13 has not been characterized, however, due to the effects of other truncation mutations downstream of K346 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function. | |
| K353Ifs*7 | frameshift | loss of function - predicted | PALB2 K353Ifs*7 indicates a shift in the reading frame starting at amino acid 353 and terminating seven residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K353Ifs*7 has not been characterized, however, due to the effects of other truncation mutations downstream of K353 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| K353Nfs*3 | frameshift | loss of function - predicted | PALB2 K353Nfs*3 indicates a shift in the reading frame starting at amino acid 353 and terminating three residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K353Nfs*3 has not been characterized, however, due to the effects of other truncation mutations downstream of K353 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| K422A | missense | unknown | PALB2 K422A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). K422A retains chromatin binding in an in vitro assay (PMID: 32041954), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| K515* | nonsense | loss of function - predicted | PALB2 K515* results in a premature truncation of the Palb2 protein at amino acid 515 of 1186 (UniProt.org). K515* has not been characterized, however, due to the effects of other truncation mutations downstream of K515 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| K515R | missense | unknown | PALB2 K515R lies within the DNA-binding region of the Palb2 protein (UniProt.org). K515R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| K628N | missense | no effect - predicted | PALB2 K628N does not lie within any known functional domains of the Palb2 protein (UniProt.org). K628N results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 35853885), and therefore, is predicted to have no effect on Palb2 protein function. | |
| K695E | missense | unknown | PALB2 K695E does not lie within any known functional domains of the Palb2 protein (UniProt.org). K695E has been identified in sequencing studies (PMID: 22842228), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| K745E | missense | unknown | PALB2 K745E does not lie within any known functional domains of the Palb2 protein (UniProt.org). K745E does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| K81R | missense | no effect - predicted | PALB2 K81R lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). K81R results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| K862Rfs*9 | frameshift | loss of function - predicted | PALB2 K862Rfs*9 indicates a shift in the reading frame starting at amino acid 862 and terminating 9 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). K862Rfs*9 has not been characterized however, due to the effects of other truncation mutations downstream of K862 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| K908fs | frameshift | loss of function - predicted | PALB2 K908fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 908 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). K908fs has not been characterized however, due to the effects of other truncation mutations downstream of K908 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| L100F | missense | unknown | PALB2 L100F lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L100F has been identified in the scientific literature (PMID: 26283626), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| L1027R | missense | loss of function | PALB2 L1027R lies within WD repeat 4 of the Palb2 protein (UniProt.org). L1027R results in decreased Palb2 protein stability, loss of nuclear localization, impaired homology-directed DNA repair activity in cultured cells, and confers sensitivity to PARP inhibition in PALB2-deficient cells (PMID: 33811135). | |
| L1040S | missense | unknown | PALB2 L1040S lies within WD repeat 4 of the Palb2 protein (UniProt.org). L1040S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| L1070P | missense | loss of function | PALB2 L1070P lies within WD repeat 5 of the Palb2 protein (UniProt.org). L1070P confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability (PMID: 31757951), aberrant cytosolic accumulation and reduced Rad51 foci formation (PMID: 31636395), and intermediate or impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 33964450, PMID: 31636395, PMID: 31757951). | |
| L1119P | missense | unknown | PALB2 L1119P lies within WD repeat 6 of the Palb2 protein (UniProt.org). L1119P results in decreased nuclear localization, Brca2 binding, and recruitment to DNA damage sites and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31586400), however, demonstrates similar Rad51 foci formation and increased Rad51 foci intensity to wild-type (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, its effect on Palb2 protein function is unknown. | |
| L1143H | missense | unknown | PALB2 L1143H lies within WD repeat 6 of the Palb2 protein (UniProt.org). L1143H does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| L1143P | missense | unknown | PALB2 L1143P lies within WD repeat 6 of the Palb2 protein (UniProt.org). The functional effect of L1143P is conflicting, as it has been reported to result in Brca2 binding similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), however, demonstrates decreased Rad51, Rad51c, and Xrcc3 binding in in vitro assays, and reduced Brca2 and Rad51c binding, decreased Rad51 foci formation, and impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 24141787), and therefore, its effect on Palb2 protein function is unknown. | |
| L1150R | missense | unknown | PALB2 L1150R lies within WD repeat 6 of the Palb2 protein (UniProt.org). L1150R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| L1172P | missense | loss of function | PALB2 L1172P lies within WD repeat 7 of the Palb2 protein (UniProt.org). L1172P confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951). | |
| L169I | missense | unknown | PALB2 L169I lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L169I demonstrates subcellular localization and recruitment to laser-induced DNA damage sites similar to wild-type Palb2, results in deceased BRCA1 binding in a mammalian two-hybrid assay, reduced RAD51 foci formation and decreased homologous repair activity in one study (PMID: 31586400), but demonstrates homologous repair activity similar to wild-type Palb2 in another study (PMID: 31636395) and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, its effect on Palb2 protein function is unknown. | |
| L17P | missense | loss of function - predicted | PALB2 L17P lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L17P results in decreased homology-directed DNA repair activity in cultured cells (PMID: 33964450), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| L21P | missense | loss of function | PALB2 L21P lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L21P results in Brca2 and Rad51 binding similar to wild-type Palb2 but fails to bind Brca1 and results in deficient Rad51 and Palb2 nuclear foci assembly (PMID: 19584259) and decreased homology-directed DNA repair in cultured cells (PMID: 19584259, PMID: 33964450). | |
| L24F | missense | loss of function | PALB2 L24F lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L24F retains binding with Rad51 but confers a loss of function to Palb2 as demonstrated by decreased homology-directed DNA repair activity and Brca1 interaction, reduced Palb2 and Rad51 foci formation, increased sensitivity to DNA damaging agents, and failure to maintain an IR-induced G2/M checkpoint in cultured cells (PMID: 35853885). | |
| L24P | missense | loss of function | PALB2 L24P lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L24P results in Brca2 and Rad51 binding similar to wild-type Palb2 but fails to bind Brca1 and results in deficient Rad51 and Palb2 nuclear foci assembly (PMID: 19584259) and decreased homology-directed DNA repair in cultured cells (PMID: 19584259, PMID: 33964450). | |
| L24S | missense | loss of function | PALB2 L24S lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L24S confers a loss of function to the Palb2 protein as demonstrated by decreased Brca1 binding and Rad51 foci formation (PMID: 31636395), and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31636395, PMID: 31757951, PMID: 33964450). | |
| L262P | missense | unknown | PALB2 L262P lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). L262P has been identified in sequencing studies (PMID: 31328403), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Dec 2023). | |
| L273R | missense | unknown | PALB2 L273R lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). L273R has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| L32V | missense | no effect - predicted | PALB2 L32V lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L32V results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| L337S | missense | no effect - predicted | PALB2 L337S lies within the DNA-binding region of the Palb2 protein (UniProt.org). L337S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951) and results in homologous recombination activity similar to wild-type protein in culture (PMID: 33169439), and therefore, is predicted to have no effect on Palb2 protein function. | |
| L35F | missense | loss of function | PALB2 L35F lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L35F retains binding with Rad51 but confers a loss of function to Palb2 as demonstrated by decreased homology-directed DNA repair activity and Brca1 interaction, reduced Palb2 and Rad51 foci formation, increased sensitivity to DNA damaging agents, and failure to maintain an IR-induced G2/M checkpoint in cultured cells (PMID: 35853885). | |
| L35P | missense | loss of function | PALB2 L35P lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L35P confers a loss of function to the Palb2 protein as demonstrated by a loss of Brca1 binding, Rad51 foci formation, and homology-directed DNA repair activity in cultured cells, and failure to rescue PARP inhibitor sensitivity in PALB2-null cells (PMID: 28319063, PMID: 31586400, PMID: 31757951). | |
| L531Cfs*30 | frameshift | loss of function | PALB2 L531Cfs*30 indicates a shift in the reading frame starting at amino acid 531 and terminating 30 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). L531Cfs*30 confers a loss of function to the Palb2 protein as demonstrated by decreased DNA binding affinity, Brca2 and Rad51 binding, and Rad51 activation in cultured cells (PMID: 28158555), and impaired homology-directed DNA repair activity compared to wild-type in a reporter assay (PMID: 33964450), and in cultured cells lacking Tp53 (PMID: 31757951). | |
| L607V | missense | unknown | PALB2 L607V does not lie within any known functional domains of the Palb2 protein (UniProt.org). L607V has not been characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| L622P | missense | unknown | PALB2 L622P does not lie within any known functional domains of the Palb2 protein (UniProt.org). L622P does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| L659Qfs*3 | frameshift | loss of function - predicted | PALB2 L659Qfs*3 indicates a shift in the reading frame starting at amino acid 659 and terminating three residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). L659Qfs*3 has not been characterized, however, due to the effects of other truncation mutations downstream of L659 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| L671* | nonsense | loss of function - predicted | PALB2 L671* results in a premature truncation of the Palb2 protein at amino acid 671 of 1186 (UniProt.org). L671* has not been characterized, however, due to the effects of other truncation mutations downstream of L671 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| L931P | missense | unknown | PALB2 L931P lies within WD repeat 2 of the Palb2 protein (UniProt.org). L931P does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| L931R | missense | no effect - predicted | PALB2 L931R lies within WD repeat 2 of the Palb2 protein (UniProt.org). L931R results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| L936S | missense | unknown | PALB2 L936S lies within WD repeat 2 of the Palb2 protein (UniProt.org). L936S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on protein function is unknown. | |
| L939W | missense | unknown | PALB2 L939W lies within WD repeat 2 of the Palb2 protein (UniProt.org). The functional effect of L939W is conflicting, as it has been reported to result in decreased Brca2, Rad51, and Xrcc3 binding in in vitro assays and a modest reduction in homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 24141787), but in another study demonstrates Brca2, Rad51, and Rad51c binding similar to wild-type Palb2 in cultured cells (PMID: 24141787, PMID: 31586400), and homology-directed DNA repair activity similar to wild-type in a reporter assay (PMID: 33964450), and in cultured cells lacking Tp53 (PMID: 27829436, PMID: 31636395, PMID: 31757951), and therefore, its effect on Palb2 protein function is unknown. | |
| L947F | missense | loss of function | PALB2 L947F lies within WD repeat 2 of the Palb2 protein (UniProt.org). L947F results in reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31586400, PMID: 31636395), Palb2 protein accumulation in the cytoplasm, and decreased Rad51 foci formation and foci intensity compared to wild-type protein (PMID: 31586400). | |
| L947S | missense | loss of function | PALB2 L947S lies within WD repeat 2 of the Palb2 protein (UniProt.org). L947S confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability, Brca2 binding, recruitment to DNA damage sites, and Rad51 foci formation and intensity, and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31586400, PMID: 31757951). | |
| L961P | missense | loss of function | PALB2 L961P lies within WD repeat 2 of the Palb2 protein (UniProt.org). L961P confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability, reduced Rad51 foci formation, and impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31757951). | |
| L972Q | missense | loss of function | PALB2 L972Q lies within WD repeat 3 of the Palb2 protein (UniProt.org). L972Q confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951). | |
| L9H | missense | unknown | PALB2 L9H lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L9H does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| L9V | missense | unknown | PALB2 L9V lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). L9V demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| loss | unknown | loss of function | PALB2 loss indicates loss of the PALB2 gene, mRNA, and protein. | |
| M1032I | missense | unknown | PALB2 M1032I lies within WD repeat 4 of the Palb2 protein (UniProt.org). M1032I has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Oct 2023). | |
| M1067T | missense | unknown | PALB2 M1067T lies within WD repeat 5 of the Palb2 protein (UniProt.org). M1067T has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| M296* | nonsense | loss of function - predicted | PALB2 M296* results in a premature truncation of the Palb2 protein at amino acid 296 of 1186 (UniProt.org). M296* has not been characterized however, due to the effects of other truncation mutations downstream of M296 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| M723Vfs*21 | frameshift | loss of function - predicted | PALB2 M723Vfs*21 indicates a shift in the reading frame starting at amino acid 723 and terminating 21 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). M723Vfs*21 has not been characterized, however, due to the effects of other truncation mutations downstream of M723 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| mutant | unknown | unknown | PALB2 mutant indicates an unspecified mutation in the PALB2 gene. | |
| N186I | missense | no effect - predicted | PALB2 N186I lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). N186I results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| N241D | missense | no effect - predicted | PALB2 N241D lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). N241D results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| N280Tfs*8 | frameshift | loss of function - predicted | PALB2 N280Tfs*8 indicates a shift in the reading frame starting at amino acid 280 and terminating 8 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). N280Tfs*8 has not been characterized however, due to the effects of other truncation mutations downstream of N280 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| N344Tfs*2 | frameshift | loss of function - predicted | PALB2 N344Tfs*2 indicates a shift in the reading frame starting at amino acid 344 and terminating two residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). N344Tfs*2 has not been characterized, however, due to the effects of other truncation mutations downstream of N344 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function. | |
| N349K | missense | unknown | PALB2 N349K lies within the DNA-binding region of the Palb2 protein (UniProt.org). N349K has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| N497Mfs*64 | frameshift | loss of function - predicted | PALB2 N497Mfs*64 indicates a shift in the reading frame starting at amino acid 497 and terminating 64 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). N497Mfs*64 results in decreased homology-directed DNA repair activity in cultured cells (PMID: 33964450), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| N716K | missense | unknown | PALB2 N716K does not lie within any known functional domains of the Palb2 protein (UniProt.org). N716K does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| N821Tfs*25 | frameshift | loss of function - predicted | PALB2 N821Tfs*25 indicates a shift in the reading frame starting at amino acid 821 and terminating 25 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). N821Tfs*25 has not been characterized however, due to the effects of other truncation mutations downstream of N821 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| N821Y | missense | no effect - predicted | PALB2 N821Y lies within a region of the Palb2 protein required for POLH interaction and POLH DNA synthesis stimulation (UniProt.org). N821Y results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| P1008L | missense | unknown | PALB2 P1008L lies within WD repeat 3 of the Palb2 protein (UniProt.org). P1008L has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P1008T | missense | unknown | PALB2 P1008T lies within WD repeat 3 of the Palb2 protein (UniProt.org). P1008T has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P1009Lfs*6 | frameshift | loss of function | PALB2 P1009Lfs*6 indicates a shift in the reading frame starting at amino acid 1009 and terminating 6 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). P1009Lfs*6 confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951). | |
| P104L | missense | loss of function | PALB2 P104L lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P104L retains the association with Brca1, Keap1, Rad51, and Rad51ap1, but results in decreased recruitment of Palb2 and Rad51 to nuclear foci, impaired homologous recombination, and failure to rescue PARP inhibitor sensitivity in PALB2-deficient cells in culture (PMID: 33169439). | |
| P1097R | missense | loss of function - predicted | PALB2 P1097R lies within WD repeat 5 of the Palb2 protein (UniProt.org). P1097R results in decreased homology-directed DNA repair activity in cultured cells (PMID: 33964450), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| P1111A | missense | unknown | PALB2 P1111A lies within the RAD51, BRCA2, and POLH-interacting regions of the Palb2 protein (UniProt.org). P1111A does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| P113Qfs*64 | frameshift | loss of function - predicted | PALB2 P113Qfs*64 indicates a shift in the reading frame starting at amino acid 113 and terminating 64 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). P113Qfs*64 has not been characterized however, due to the effects of other truncation mutations downstream of P113 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| P187L | missense | unknown | PALB2 P187L lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P187L has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P191S | missense | unknown | PALB2 P191S lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P191S has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P207R | missense | no effect - predicted | PALB2 P207R lies within the DNA-binding, and BRCA1-interacting regions of the Palb2 protein (UniProt.org). P207R results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| P210L | missense | no effect | PALB2 P210L lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). P210L retains homology-directed DNA repair activity in cultured cells (PMID: 31636395, PMID: 31757951), results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400) | |
| P249H | missense | unknown | PALB2 P249H lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). P249H has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P378Lfs*46 | frameshift | loss of function - predicted | PALB2 P378Lfs*46 indicates a shift in the reading frame starting at amino acid 378 and terminating 46 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). P378Lfs*46 has not been characterized, however, due to the effects of other truncation mutations downstream of P378 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| P405A | missense | no effect - predicted | PALB2 P405A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). P405A demonstrates homology-directed DNA repair activity similar to wild-type in cultured cells (PMID: 33811135, PMID: 35853885), and therefore, is predicted to have no effect on Palb2 protein function. | |
| P405T | missense | unknown | PALB2 P405T lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). P405T demonstrates chromatin association similar to wild-type Palb2 in cell culture (PMID: 29387807), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| P490A | missense | no effect - predicted | PALB2 P490A lies within the DNA-binding region of the Palb2 protein (UniProt.org). P490A results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| P4L | missense | no effect - predicted | PALB2 P4L lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P4L results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| P4S | missense | unknown | PALB2 P4S lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P4S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| P5S | missense | unknown | PALB2 P5S lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P5S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| P615S | missense | unknown | PALB2 P615S does not lie within any known functional domains of the Palb2 protein (UniProt.org). P615S demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| P65L | missense | no effect - predicted | PALB2 P65L lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P65L demonstrates BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| P707L | missense | no effect - predicted | PALB2 P707L does not lie within any known functional domains of the Palb2 protein (UniProt.org). P707L results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| P729H | missense | unknown | PALB2 P729H does not lie within any known functional domains of the Palb2 protein (UniProt.org). P729H has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P758L | missense | unknown | PALB2 P758L does not lie within any known functional domains of the Palb2 protein (UniProt.org). P758L has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P812L | missense | unknown | PALB2 P812L lies within a region of the Palb2 protein required for POLH interaction and POLH DNA synthesis stimulation (UniProt.org). P812L has not been characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| P864S | missense | no effect | PALB2 P864S lies within WD repeat 1 of the Palb2 protein (UniProt.org). P864S results in Brca2 binding, Rad51 foci formation, and recruitment to DNA damage sites similar to wild-type Palb2 in cultured cells (PMID: 31586400), retains homology-directed DNA repair activity in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 31757951), and rescues PARP inhibitor sensitivity in PALB2-null cells (PMID: 31586400). | |
| P8L | missense | unknown | PALB2 P8L lies within the DNA-binding and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). P8L demonstrates subcellular localization, recruitment to DNA damage sites, and Brca1 binding similar to wild-type Palb2 (PMID: 31586400), and leads to homology-directed DNA repair activity similar to wild-type Palb2 in one study (PMID: 31636395), but results in impaired homology-directed DNA repair activity, reduced Rad51 foci formation, and fails to rescue PARP inhibitor sensitivity in PALB2-null cells in another study (PMID: 31586400), and therefore, its effect on Palb2 protein function is unknown. | |
| Q1023* | nonsense | loss of function - predicted | PALB2 Q1023* results in a premature truncation of the Palb2 protein at amino acid 1023 of 1186 (UniProt.org). Q1023* has not been characterized however, due to the effects of other truncation mutations downstream of Q1023 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| Q1044H | missense | unknown | PALB2 Q1044H lies within WD repeat 4 of the Palb2 protein (UniProt.org). Q1044H demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| Q1056* | nonsense | loss of function - predicted | PALB2 Q1056* results in a premature truncation of the Palb2 protein at amino acid 1056 of 1186 (UniProt.org). Q1056* has not been characterized, however, due to the effects of other truncation mutations downstream of Q1056 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| Q1114H | missense | no effect - predicted | PALB2 Q1114H lies within the RAD51, BRCA2, and POLH-interacting region of the Palb2 protein (UniProt.org). Q1114H results in Brca2 binding similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), and therefore, is predicted to have no effect on protein function. | |
| Q151* | nonsense | loss of function - predicted | PALB2 Q151* results in a premature truncation of the Palb2 protein at amino acid 151 of 1186 (UniProt.org). Q151* has not been characterized however, due to the effects of other truncation mutations downstream of Q151 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| Q251* | nonsense | loss of function - predicted | PALB2 Q251* results in a premature truncation of the Palb2 protein at amino acid 251 of 1186 (UniProt.org). Q251* results in impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| Q348* | nonsense | loss of function - predicted | PALB2 Q348* results in a premature truncation of the Palb2 protein at amino acid 348 of 1186 (UniProt.org). Q348* has not been characterized, however, due to the effects of other truncation mutations downstream of Q348 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| Q348K | missense | loss of function - predicted | PALB2 Q348K lies within the DNA-binding region of the Palb2 protein (UniProt.org). Q348K results in similar expression, nuclear localization, and interaction with Brca1 to wild-type Palb2, but leads to a partial reduction in homologous recombination activity in cell culture (PMID: 35762214), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| Q39L | missense | unknown | PALB2 Q39L lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). Q39L demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| Q420A | missense | unknown | PALB2 Q420A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). Q420A retains chromatin binding in an in vitro assay (PMID: 32041954), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| Q559R | missense | no effect | PALB2 Q559R lies within the DNA-binding region of the Palb2 protein (UniProt.org). Q559R is a common Palb2 polymorphism (PMID: 23977390, PMID: 21165770), results in homologous recombination similar to wild-type Palb2 (PMID: 33169439, PMID: 33964450) and does not demonstrate reduced homology-directed DNA repair activity in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951). | |
| Q60Rfs*7 | frameshift | loss of function | PALB2 Q60Rfs*7 indicates a shift in the reading frame starting at amino acid 60 and terminating 7 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). Q60Rfs*7 confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951). | |
| Q775* | nonsense | loss of function | PALB2 Q775* results in a premature truncation of the Palb2 protein at amino acid 775 of 1186 (UniProt.org). Q775* confers a loss of function to the Palb2 protein as demonstrated by loss of Poln foci formation (PMID: 24485656), and decreased Brca2 and Rad51 binding and reduced Rad51 activation in cultured cells (PMID: 28158555). | |
| Q790* | nonsense | loss of function - predicted | PALB2 Q790* results in a premature truncation of the Palb2 protein at amino acid 790 of 1186 (UniProt.org). Q790* has not been characterized, however, due to the effects of other truncation mutations downstream of Q790 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| Q921Tfs*7 | frameshift | loss of function - predicted | PALB2 Q921Tfs*7 indicates a shift in the reading frame starting at amino acid 921 and terminating seven residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). Q921Tfs*7 has not been characterized however, due to the effects of other truncation mutations downstream of Q921 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| Q958P | missense | unknown | PALB2 Q958P lies within WD repeat 2 of the Palb2 protein (UniProt.org). Q958P does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| Q988* | nonsense | loss of function | PALB2 Q988* results in a premature truncation of the Palb2 protein at amino acid 988 of 1186 (UniProt.org). Q988* confers a loss of function to the Palb2 protein as demonstrated by aberrant cytosolic accumulation in cultured cells (PMID: 28158555), and reduced protein stability and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951). | |
| R1086* | nonsense | loss of function - predicted | PALB2 R1086* indicates a premature truncation of the Palb2 protein at amino acid 1086 of 1186 (UniProt.org). R1086* results in impaired homologous recombination in cultured cells (PMID: 33169439), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| R1086Efs*9 | frameshift | loss of function - predicted | PALB2 R1086Efs*9 indicates a shift in the reading frame starting at amino acid 1086 and terminating 9 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). R1086Efs*9 has not been characterized, however, due to the effects of other truncation mutations downstream of R1086 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function. | |
| R131fs | frameshift | loss of function - predicted | PALB2 R131fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 131 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). R131fs has not been characterized however, due to the effects of other truncation mutations downstream of R131 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| R153W | missense | no effect - predicted | PALB2 R153W lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R153W results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 35853885), and therefore, is predicted to have no effect on Palb2 protein function. | |
| R170Ifs*14 | frameshift | loss of function | PALB2 R170Ifs*14 indicates a shift in the reading frame starting at amino acid 170 and terminating 14 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). R170Ifs*14 confers a loss of function to the Palb2 protein as demonstrated by decreased recruitment to DNA damage sites, reduced Brca2 binding, and loss of Rad51 activation in cultured cells (PMID: 28158555). | |
| R34C | missense | unknown | PALB2 R34C lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R34C does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| R34H | missense | unknown | PALB2 R34H lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R34H does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| R37C | missense | unknown | PALB2 R37C lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R37C results in homology-directed DNA repair activity similar to wild-type in cultured cells in one study (PMID: 31636395), but decreased homology-directed DNA repair activity in another study (PMID: 33811135), and therefore, its effect on Palb2 protein function is unknown. | |
| R37H | missense | unknown | PALB2 R37H lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R37H results in decreased Brca1 binding and recruitment to DNA damage sites (PMID: 31757951), reduced Rad51 foci formation and intensity (PMID: 31586400), impaired homology-directed DNA repair activity, and failure to rescue PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 28319063, PMID: 31586400, PMID: 31757951), but in other studies demonstrates Brca1 binding and recruitment to DNA damage sites similar to wild-type Palb2 (PMID: 28319063, PMID: 31586400), and homology-directed DNA repair similar to wild-type in a reporter assay (PMID: 33964450), and therefore, its effect on Palb2 protein function is unknown. | |
| R37P | missense | unknown | PALB2 R37P lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R37P results in intermediate homology-directed DNA repair activity in cultured cells (PMID: 33964450), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| R37S | missense | no effect - predicted | PALB2 R37S lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). R37S results in homology-directed DNA repair similar to wild-type Palb2 in cultured cells (PMID: 31636395, PMID: 33964450), and therefore, is predicted to have no effect on Palb2 protein function. | |
| R414* | nonsense | loss of function - predicted | PALB2 R414* results in a premature truncation of the Palb2 protein at amino acid 414 of 1186 (UniProt.org). R414* has not been characterized however, due to the effects of other truncation mutations downstream of R414 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| R414A | missense | loss of function - predicted | PALB2 R414A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). R414A results in loss of chromatin binding in an in vitro assay (PMID: 32041954), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| R414K | missense | loss of function - predicted | PALB2 R414K lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). R414K results in loss of chromatin binding in an in vitro assay (PMID: 32041954), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| R414Q | missense | loss of function - predicted | PALB2 R414Q lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). R414Q results in decreased chromatin binding in an in vitro assay (PMID: 32041954), and therefore, is predicted to lead to a loss of Palb2 protein function | |
| R421A | missense | loss of function - predicted | PALB2 R421A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). R421A results in decreased chromatin binding in an in vitro assay (PMID: 32041954), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| R421K | missense | unknown | PALB2 R421K lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). R421K retains chromatin binding in an in vitro assay (PMID: 32041954), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| R566H | missense | unknown | PALB2 R566H lies within the DNA-binding region of the Palb2 protein (UniProt.org). R566H has been identified in sequencing studies (PMID: 22895193, PMID: 26000489), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| R594K | missense | unknown | PALB2 R594K does not lie within any known functional domains of the Palb2 protein (UniProt.org). R594K has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Dec 2023). | |
| R663C | missense | no effect - predicted | PALB2 R663C does not lie within any known functional domains of the Palb2 protein (UniProt.org). R663C results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 35853885), and therefore, is predicted to have no effect on Palb2 protein function. | |
| R753* | nonsense | loss of function - predicted | PALB2 R753* indicates a premature truncation of the Palb2 protein at amino acid 753 of 1186 (UniProt.org). R753* results in impaired homologous recombination in cultured cells (PMID: 33169439), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| R753Q | missense | unknown | PALB2 R753Q does not lie within any known functional domains of the Palb2 protein (UniProt.org). R753Q has been identified in the scientific literature (PMID: 24728327, PMID: 26343386, PMID: 34635506), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| S1058P | missense | no effect - predicted | PALB2 S1058P lies within WD repeat 5 of the Palb2 protein (UniProt.org). S1058P results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| S1075G | missense | no effect - predicted | PALB2 S1075G lies within WD repeat 5 of the Palb2 protein (UniProt.org). S1075G results in BRCA2-binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| S1084L | missense | no effect - predicted | PALB2 S1084L lies within WD repeat 5 of the Palb2 protein (UniProt.org). S1084L results in BRCA2-binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| S1102R | missense | unknown | PALB2 S1102R lies within WD repeat 5 of the Palb2 protein (UniProt.org). S1102R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S1160P | missense | unknown | PALB2 S1160P lies within WD repeat 7 of the Palb2 protein (UniProt.org). S1160P does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S1165L | missense | unknown | PALB2 S1165L lies within WD repeat 7 of the Palb2 protein (UniProt.org). S1165L does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on protein function is unknown. | |
| S1169C | missense | unknown | PALB2 S1169C lies within WD repeat 7 of the Palb2 protein (UniProt.org). S1169C retains homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S172fs | frameshift | loss of function | PALB2 S172fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 172 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). S172fs confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951). | |
| S254Ifs*3 | frameshift | loss of function - predicted | PALB2 S254Ifs*3 indicates a shift in the reading frame starting at amino acid 254 and terminating 3 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). S254Ifs*3 has not been characterized, however, due to the effects of other truncation mutations downstream of S254 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function. | |
| S319Y | missense | no effect - predicted | PALB2 S319Y lies within the DNA-binding, and BRCA1-interacting regions of the Palb2 protein (UniProt.org). S319Y results in reduced BRCA1 binding in a mammalian two-hybrid assay and decreased RAD51 foci formation in culture, but demonstrates subcellular localization, recruitment to laser-induced DNA damage sites (PMID: 31586400), and homologous recombination activity similar to wild-type Palb2 (PMID: 31636395, PMID: 31586400), and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore is predicted to have no effect on Palb2 protein function. | |
| S382I | missense | unknown | PALB2 S382I lies within the DNA-binding region of the Palb2 protein (UniProt.org). S382I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S387Lfs*14 | frameshift | loss of function - predicted | PALB2 S387Lfs*14 indicates a shift in the reading frame starting at amino acid 387 and terminating 14 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). S387Lfs*14 has not been characterized, however, due to the effects of other truncation mutations downstream of S387 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| S417A | missense | loss of function - predicted | PALB2 S417A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). S417A results in decreased chromatin binding in an in vitro assay (PMID: 32041954), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| S417Y | missense | no effect - predicted | PALB2 S417Y lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). S417Y results in reduced chromatin interaction compared to wild-type Palb2 (PMID: 29387807), however, demonstrates Rad51 foci formation and cell survival in response to genotoxic stress similar to wild-type in cultured cells (PMID: 29387807), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| S474N | missense | unknown | PALB2 S474N lies within the DNA-binding region of the Palb2 protein (UniProt.org). S474N does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S578G | missense | unknown | PALB2 S578G lies within the DNA-binding region of the Palb2 protein (UniProt.org). S578G does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S64L | missense | loss of function | PALB2 S64L lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). S64L retains the association with Brca1, Keap1, Rad51, and Rad51ap1, but results in decreased recruitment of Palb2 and Rad51 to nuclear foci, impaired homologous recombination, and failure to rescue PARP inhibitor sensitivity in PALB2-deficient cells in culture (PMID: 33169439). | |
| S779* | nonsense | loss of function - predicted | PALB2 S779* results in a premature truncation of the Palb2 protein at amino acid 779 of 1186 (UniProt.org). S779* has not been characterized, however, due to the effects of other truncation mutations downstream of S779 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| S835P | missense | unknown | PALB2 S835P lies within a region of the Palb2 protein required for POLH interaction and POLH DNA synthesis stimulation (UniProt.org). S835P has not been characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| S859* | nonsense | loss of function - predicted | PALB2 S859* results in a premature truncation of the Palb2 protein at amino acid 859 of 1186 (UniProt.org). S859* has not been characterized however, due to the effects of other truncation mutations downstream of S859 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| S865P | missense | unknown | PALB2 S865P lies within WD repeat 1 of the Palb2 protein (UniProt.org). S865P does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S896F | missense | unknown | PALB2 S896F lies within WD repeat 1 of the Palb2 protein (UniProt.org). S896F demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| S951F | missense | unknown | PALB2 S951F lies within WD repeat 2 of the Palb2 protein (UniProt.org). S951F does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on protein function is unknown. | |
| S955R | missense | no effect - predicted | PALB2 S955R lies within WD repeat 2 of the Palb2 protein (UniProt.org). S955R results in BRCA2 binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| S979Vfs*11 | frameshift | loss of function - predicted | PALB2 S979Vfs*11 indicates a shift in the reading frame starting at amino acid 979 and terminating 11 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). S979Vfs*11 has not been characterized however, due to the effects of other truncation mutations downstream of S979 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function. | |
| T1012I | missense | no effect - predicted | PALB2 T1012I lies within WD repeat 4 of the Palb2 protein (UniProt.org). T1012I demonstrates homology-directed DNA repair activity similar to wild-type in cultured cells (PMID: 33811135, PMID: 35853885), and therefore, is predicted to have no effect on Palb2 protein function. | |
| T1030I | missense | loss of function | PALB2 T1030I lies within WD repeat 4 of the Palb2 protein (UniProt.org). T1030I confers a loss of function to the Palb2 protein as demonstrated by reduced Rad51 and Rad51c binding in in vitro assays (PMID: 24141787), decreased protein stability (PMID: 24141787, PMID: 31757951), reduced Rad51 foci formation, loss of Brca2 binding, and aberrant cytoplasmic localization (PMID: 31586400), and impaired homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 31757951). | |
| T1099M | missense | no effect - predicted | PALB2 T1099M lies within WD repeat 5 of the Palb2 protein (UniProt.org). T1099M results in homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells (PMID: 35853885), and therefore, is predicted to have no effect on Palb2 protein function. | |
| T1099R | missense | unknown | PALB2 T1099R lies within WD repeat 5 of the Palb2 protein (UniProt.org). T1099R does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T1167I | missense | unknown | PALB2 T1167I lies within WD repeat 7 of the Palb2 protein (UniProt.org). T1167I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T124I | missense | no effect - predicted | PALB2 T124I lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). T124I results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| T226S | missense | unknown | PALB2 T226S lies within the DNA-binding and BRCA1-interacting regions of the Palb2 protein (UniProt.org). T226S has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Mar 2024). | |
| T317P | missense | no effect - predicted | PALB2 T317P lies within the DNA-binding, and BRCA1-interacting regions of the Palb2 protein (UniProt.org). T317P results in BRCA1 binding similar to wild-type Palb2 in a mammalian two-hybrid assay, and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| T31I | missense | unknown | PALB2 T31I lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). T31I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T333A | missense | unknown | PALB2 T333A lies within the DNA-binding region of the Palb2 protein (UniProt.org). T333A has been identified in sequencing studies (PMID: 31328403), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Dec 2023). | |
| T351Rfs*4 | frameshift | loss of function - predicted | PALB2 T351Rfs*4 indicates a shift in the reading frame starting at amino acid 351 and terminating four residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). T351Rfs*4 has not been characterized, however, due to the effects of other truncation mutations downstream of T351 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| T397I | missense | unknown | PALB2 T397I lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T397I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T397S | missense | unknown | PALB2 T397S lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T397S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395) and demonstrates chromatin association similar to wild-type Palb2 in cell culture (PMID: 29387807), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T413A | missense | loss of function - predicted | PALB2 T413A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T413A results in decreased chromatin binding in an in vitro assay (PMID: 32041954), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| T413Hfs*11 | frameshift | loss of function - predicted | PALB2 T413Hfs*11 indicates a shift in the reading frame starting at amino acid 413 and terminating 11 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). T413Hfs*11 has not been characterized however, due to the effects of other truncation mutations downstream of T413 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| T413K | missense | unknown | PALB2 T413K lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T413K does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T413S | missense | loss of function | PALB2 T413S lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). T413S results in impaired chromatin binding (PMID: 29387807, PMID: 32041954), supports Rad51 foci but not gamma-H2AX foci formation in response to genotoxic stress, and fails to rescue genotoxic sensitivity in PALB2-null cells in culture (PMID: 29387807). | |
| T494Lfs*67 | frameshift | loss of function - predicted | PALB2 T494Lfs*67 indicates a shift in the reading frame starting at amino acid 494 and terminating 67 residues downstream causing a premature truncation of the 1186 amino acid Palb2 protein (UniProt.org). T494Lfs*67 has not been characterized, however, due to the effects of other Palb2 truncation mutations downstream of T494 (PMID: 31757951, PMID: 31636395), is predicted to lead to a loss of Palb2 protein function. | |
| T706I | missense | unknown | PALB2 T706I does not lie within any known functional domains of the Palb2 protein (UniProt.org). T706I does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T733A | missense | unknown | PALB2 T733A does not lie within any known functional domains of the Palb2 protein (UniProt.org). T733A has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| T734S | missense | unknown | PALB2 T734S does not lie within any known functional domains of the Palb2 protein (UniProt.org). T734S does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| T993M | missense | unknown | PALB2 T993M lies within WD repeat 3 of the Palb2 protein (UniProt.org). T993M demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V1019A | missense | unknown | PALB2 V1019A lies within WD repeat 4 of the Palb2 protein (UniProt.org). V1019A does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V1036A | missense | unknown | PALB2 V1036A lies within WD repeat 4 of the Palb2 protein (UniProt.org). V1036A demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V1103L | missense | unknown | PALB2 V1103L lies within WD repeat 5 of the Palb2 protein (UniProt.org). V1103L does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V1103M | missense | unknown | PALB2 V1103M lies within WD repeat 5 of the Palb2 protein (UniProt.org). V1103M does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V1105A | missense | no effect - predicted | PALB2 V1105A lies within WD repeat 5 of the Palb2 protein (UniProt.org). V1105A results in BRCA2-binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400), and therefore, is predicted to have no effect on Palb2 protein function. | |
| V1123M | missense | unknown | PALB2 V1123M lies within WD repeat 6 of the Palb2 protein (UniProt.org). V1123M does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V1154L | missense | unknown | PALB2 V1154L lies within the WD repeat 7 of the Palb2 protein (UniProt.org). V1154L has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Mar 2024). | |
| V410A | missense | loss of function - predicted | PALB2 V410A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). V410A results in decreased chromatin binding in an in vitro assay (PMID: 32041954), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| V410G | missense | unknown | PALB2 V410G lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). V410G results in chromatin binding similar to wild-type Palb2 in cultured cells (PMID: 29387807), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V425A | missense | unknown | PALB2 V425A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). V425A retains chromatin binding in an in vitro assay (PMID: 32041954), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V425M | missense | unknown | PALB2 V425M lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). V425M results in chromatin binding similar to wild-type Palb2 in cultured cells (PMID: 29387807, PMID: 32041954), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V428A | missense | unknown | PALB2 V428A lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). V428A retains chromatin binding in an in vitro assay (PMID: 32041954), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| V487D | missense | unknown | PALB2 V487D lies within the DNA-binding region of the Palb2 protein (UniProt.org). V487D has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| V78I | missense | no effect | PALB2 V78I lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). V78I demonstrates homology-directed DNA repair activity comparable to wild-type Palb2 in culture (PMID: 31636395), and results in BRCA2-binding similar to wild-type Palb2 in a mammalian two-hybrid assay and rescues PARP inhibitor sensitivity in PALB2-null cells in culture (PMID: 31586400). | |
| V858L | missense | unknown | PALB2 V858L lies within WD repeat 1 of the Palb2 protein (UniProt.org). V858L has been identified in sequencing studies (PMID: 29285234), but has not been biochemically characterized and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| V917D | missense | unknown | PALB2 V917D lies within WD repeat 2 of the Palb2 protein (UniProt.org). V917D has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| V932A | missense | unknown | PALB2 V932A lies within WD repeat 2 of the Palb2 protein (UniProt.org). V932A has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| V932M | missense | no effect | PALB2 V932M lies within WD repeat 2 of the Palb2 protein (UniProt.org). V932M results in Brca2 binding, Rad51 foci formation, and recruitment to DNA damage sites similar to wild-type Palb2 in cultured cells (PMID: 31586400), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31586400, PMID: 31636395, PMID: 33964450). | |
| W1038* | nonsense | loss of function | PALB2 W1038* results in a premature truncation of the Palb2 protein at amino acid 1038 of 1186 (UniProt.org). W1038* confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability (PMID: 31757951), aberrant cytosolic accumulation, decreased Brca2 binding and Rad51 foci formation (PMID: 28158555), and impaired homologous recombination in cultured cells (PMID: 28158555, PMID: 31757951). | |
| W1140G | missense | loss of function - predicted | PALB2 W1140G lies within WD repeat 6 of the Palb2 protein (UniProt.org). W1140G does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), however, results in decreased Brca2 binding, reduced Rad51 foci formation, aberrant cytoplasmic localization, and impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31586400), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| W1159L | missense | unknown | PALB2 W1159L lies within WD repeat 7 of the Palb2 protein (UniProt.org). W1159L does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| W1164C | missense | unknown | PALB2 W1164C lies within WD repeat 7 of the Palb2 protein (UniProt.org). W1164C does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| W898* | nonsense | loss of function - predicted | PALB2 W898* results in a premature truncation of the Palb2 protein at amino acid 898 of 1186 (UniProt.org). W898* has not been characterized however, due to the effects of other truncation mutations downstream of W898 (PMID: 31636395, PMID: 31757951), is predicted to lead to a loss of Palb2 protein function. | |
| W912G | missense | loss of function | PALB2 W912G lies within WD repeat 1 of the Palb2 protein (UniProt.org). W912G confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability, reduced Rad51 foci formation, and impaired homology-directed DNA repair activity compared to wild-type in cultured cells (PMID: 31757951). | |
| wild-type | none | no effect | Wild-type PALB2 indicates that no mutation has been detected within the PALB2 gene. | |
| Y1064C | missense | no effect - predicted | PALB2 Y1064C lies within WD repeat 5 of the Palb2 protein (UniProt.org). Y1064C results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| Y1108fs | frameshift | loss of function - predicted | PALB2 Y1108fs results in a change in the amino acid sequence of the Palb2 protein beginning at aa 1108 of 1186, likely resulting in premature truncation of the functional protein (UniProt.org). Y1108fs results in impaired homology-directed DNA repair activity similar to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), and therefore, is predicted to lead to a loss of protein function. | |
| Y1183* | nonsense | loss of function | PALB2 Y1183* results in a premature truncation of the Palb2 protein at amino acid 1183 of 1186 (UniProt.org). Y1183* confers a loss of function to the Palb2 protein as demonstrated by decreased protein stability (PMID: 31757951), and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951). | |
| Y1183C | missense | unknown | PALB2 Y1183C lies within WD repeat 7 of the Palb2 protein (UniProt.org). Y1183C does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| Y1185S | missense | unknown | PALB2 Y1185S lies within WD repeat 7 of the Palb2 protein (UniProt.org). Y1185S has not been characterized in the scientific literature and therefore, its effect on Palb2 protein function is unknown (PubMed, Nov 2023). | |
| Y28C | missense | unknown | PALB2 Y28C lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). Y28C results in decreased Brca1 binding and Rad51 foci formation (PMID: 28319063, PMID: 31586400), and impaired homology-directed DNA repair activity in cultured cells in one study (PMID: 28319063, PMID: 31586400, PMID: 31757951), but results in intermediate homology-directed DNA repair in a reporter assay (PMID: 33964450), and rescues PARP inhibitor sensitivity in PALB2-null cells (PMID: 31586400), and therefore, its effect on Palb2 protein function is unknown. | |
| Y28P | missense | loss of function - predicted | PALB2 Y28P lies within the DNA-binding, and BRCA1 and RAD51-interacting regions of the Palb2 protein (UniProt.org). Y28P results in decreased homology-directed DNA repair activity in cultured cells (PMID: 33964450), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| Y408H | missense | no effect - predicted | PALB2 Y408H lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). Y408H results in DNA damage-induced cell cycle checkpoint maintenance similar to wild-type Palb2 (PMID: 31757951), and does not demonstrate reduced homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951), and therefore, is predicted to have no effect on Palb2 protein function. | |
| Y409* | nonsense | loss of function - predicted | PALB2 Y409* results in a premature truncation of the Palb2 protein at amino acid 409 of 1186 (UniProt.org). Y409* results in protein expression similar to wild-type Palb2, however, demonstrates impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31757951), and therefore, is predicted to lead to a loss of Palb2 protein function. | |
| Y409C | missense | unknown | PALB2 Y409C lies within the DNA-binding and chromatin-association motif regions of the Palb2 protein (UniProt.org). Y409C demonstrates homology-directed DNA repair activity in cultured cells (PMID: 33811135), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown. | |
| Y551* | nonsense | loss of function | PALB2 Y551* results in a premature truncation of the Palb2 protein at amino acid 551 of 1186 (UniProt.org). Y551* confers a loss of function to the Palb2 protein as demonstrated by loss of Brca2 and Rad51c binding and reduced Rad51 binding in cultured cells (PMID: 24141787), and impaired homology-directed DNA repair activity compared to wild-type in cultured cells lacking Tp53 (PMID: 31636395, PMID: 31757951). |
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