BRCA2
Chr 13ADSomaticARBRCA2 DNA repair associated
Also known as: BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD, FANCD1, GLM3
The BRCA2 protein functions in homologous recombination DNA repair by binding RAD51 and promoting its assembly onto single-stranded DNA at double-strand breaks. Biallelic mutations cause Fanconi anemia complementation group D1, while heterozygous mutations predispose to familial breast-ovarian cancer syndrome and increase susceptibility to various cancers including medulloblastoma, glioblastoma, pancreatic cancer, and Wilms tumor. The gene follows autosomal recessive inheritance for Fanconi anemia and autosomal dominant inheritance with reduced penetrance for cancer predisposition syndromes.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
1000 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 107 | 0 | 4 | 0 | 111 |
Likely Pathogenic | 21 | 3 | 2 | 0 | 26 |
VUS | 5 | 329 | 19 | 2 | 355 |
Likely Benign | 1 | 31 | 59 | 399 | 490 |
Benign | 0 | 6 | 1 | 0 | 7 |
Conflicting | — | 11 | |||
| Total | 134 | 369 | 85 | 401 | 1,000 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
BRCA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
ScreenIng of Genetic Susceptibility Genes for Breast Cancer Patients in CHinese communiTies
RECRUITINGAssessing Clinical Features and Outcome of Breast Cancer in PALB2 Mutation Carriers: the Palbreast Study
RECRUITINGComprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO
ACTIVE NOT RECRUITINGA Prospective Registry for Patients at High-Risk for Pancreatic Cancer
RECRUITINGPembrolizumab in Treating Participants With Metastatic, Recurrent or Locally Advanced Cancer and Genomic Instability
ACTIVE NOT RECRUITINGPhase Ib Study of Axatilimab in Combination With Olaparib in BRCA1/2 and PALB2- Associated Metastatic HER2-negative Breast Cancer
RECRUITINGCombination Therapy in Cancers With Mutations in DNA Repair Genes
RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGPROMISE Registry: A Prostate Cancer Registry of Outcomes and Germline Mutations for Improved Survival and Treatment Effectiveness
RECRUITINGThe PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer
ACTIVE NOT RECRUITINGKPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
RECRUITINGProspective Study of MAstectomy With Reconstruction Including Robot Endoscopic Surgery
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools