BRCA2
Chr 13ADSomaticARBRCA2 DNA repair associated
Also known as: BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD, FANCD1, GLM3
Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, May 2020]
Primary Disease Associations & Inheritance
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
700 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 | 105 | 1 | 35 | 0 | 141 |
Likely Pathogenic | 11 | 0 | 3 | 0 | 14 |
VUS | 5 | 306 | 29 | 4 | 344 |
Likely Benign | 1 | 20 | 53 | 119 | 193 |
Benign | 0 | 2 | 3 | 0 | 5 |
Conflicting | — | 3 | |||
| Total | 122 | 329 | 123 | 123 | 700 |
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.
Gene2Phenotype Curations
Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Saruparib (AZD5305) Plus Camizestrant Compared With CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer
RECRUITINGIdentification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma
ACTIVE NOT RECRUITINGTesting the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial
RECRUITINGNGS-based Germline and Somatic Genetic Test in Ovarian Carcinoma
ACTIVE NOT RECRUITINGThe PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment
RECRUITINGOlaparib and Durvalumab (MEDI4736) in Patients with Metastatic Pancreatic Cancer and DNA Damage Repair Genes Alterations
ACTIVE NOT RECRUITINGStudy of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene Alterations
RECRUITINGA Prospective CohorT Study of HandX - Assisted ENdoscopic MAstectomy: Feasibility and Safety (ATHENA I Study)
RECRUITINGEndocrine Disruptors and Life STILe in Breast Cancer Development
ACTIVE NOT RECRUITINGInvestigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
ACTIVE NOT RECRUITINGPancreatic Cancer Genetics
RECRUITINGAnalysing Outcomes After Prostate Cancer Diagnosis and Treatment in Carriers of Rare Germline Mutations
RECRUITINGExternal Resources
Links to major genomics databases and tools