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Gene | BARD1 |
Variant | G451fs |
Impact List | frameshift |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | BARD1 G451fs results in a change in the amino acid sequence of the Bard1 protein beginning at aa 451 of 777, likely resulting in premature truncation of the functional protein (UniProt.org). G451fs has been associated with increased loss of heterozygosity (LOH) in patient samples, and is predicted to confer a loss of function to the Bard1 protein as demonstrated by decreased homology-directed DNA repair activity in cell culture (PMID: 30925164). |
Associated Drug Resistance | |
Category Variants Paths |
BARD1 mutant BARD1 inact mut BARD1 G451fs |
Transcript | NM_000465.4 |
gDNA | chr2:g.(214769276_214769277) |
cDNA | c.(1351_1350) |
Protein | p.G451fs |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000465.4 | chr2:g.(214769276_214769277) | c.(1351_1350) | p.G451fs | RefSeq | GRCh38/hg38 |
NM_000465 | chr2:g.(214769276_214769277) | c.(1351_1350) | p.G451fs | RefSeq | GRCh38/hg38 |
NM_000465.3 | chr2:g.(214769276_214769277) | c.(1351_1350) | p.G451fs | RefSeq | GRCh38/hg38 |
XM_047445350.1 | chr2:g.(214769276_214769277) | c.(1351_1350) | p.G451fs | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 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 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 |