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Gene | BARD1 |
Variant | D135N |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | BARD1 D135N lies within the RAD51-interacting domain of the Bard1 protein (PMID: 28976962). D135N results in Brca1 interaction similar to wild-type Bard1 but decreased Rad51 interaction and increased sensitivity to DNA damage upon irradiation in culture and in mouse models (PMID: 33933153). |
Associated Drug Resistance | |
Category Variants Paths |
BARD1 mutant BARD1 inact mut BARD1 D135N |
Transcript | NM_000465.4 |
gDNA | chr2:g.214781471C>T |
cDNA | c.403G>A |
Protein | p.D135N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017004613.2 | chr2:g.214792357C>T | c.403G>A | p.D135N | RefSeq | GRCh38/hg38 |
XM_017004614.2 | chr2:g.214792357C>T | c.403G>A | p.D135N | RefSeq | GRCh38/hg38 |
NM_000465.4 | chr2:g.214781471C>T | c.403G>A | p.D135N | RefSeq | GRCh38/hg38 |
NM_000465.3 | chr2:g.214781471C>T | c.403G>A | p.D135N | RefSeq | GRCh38/hg38 |
XM_047445350.1 | chr2:g.214781471C>T | c.403G>A | p.D135N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BARD1 inact mut | colorectal cancer | predicted - sensitive | Veliparib | Preclinical - Cell culture | Actionable | In a preclinical study, a colorectal cancer cell line over expressing the BARD1-beta splice variant, which results in decreased Brca1 function, demonstrated sensitivity to treatment with Veliparib (ABT-888) in culture, resulting in increased apoptotic activity (PMID: 27197561). | 27197561 |
BARD1 inact mut | prostate cancer | sensitive | Olaparib | Guideline | Actionable | Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in BARD1 (NCCN.org). | detail... |
BARD1 inact mut | prostate cancer | sensitive | Olaparib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including BARD1 (PMID: 32343890; NCT02987543). | detail... 32343890 detail... |
BARD1 mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline BARD1 mutations are associated with increased risk of developing breast cancer (NCCN.org). | detail... |
BARD1 mutant | breast cancer | no benefit | Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment did not result in an objective response in a patient with metastatic breast cancer harboring a germline mutation in BARD1 (PMID: 33119476; NCT03344965). | 33119476 |