Alt. symbols: FANCD1 | FACD | FANCD | FAD | FAD1 | BRCC2 | XRCC11

Approved name: BRCA2 DNA repair associated
Alt. names: Fanconi anemia, complementation group D1, breast cancer 2, early onset, breast cancer 2 | BRCA1/BRCA2-containing complex, subunit 2

Location: 13q13.1: 32315086 - 32400268 (+)
Gene type: protein_coding, 19 transcripts.

Scores: LoFtool: 0.089600 | pLI: 0.00000000 | LOEUF: 0.635

HGNC: 1101

NCBI: 675, RefSeq: NG_012772.3

Ensembl: ENSG00000139618.19

LRG_293 | Status: public

OMIM: 600185

Expression | ProteinAtlas

The BRCA2 gene is located on chromosome 13q and consists of 26 coding exons which code for a protein of 3,418 amino acids. There are eight copies of 30 to 80 amino acid repeats (the BRC motif) in the central third of the protein. These regions mediate binding to the RAD51 recombinase, which functions in DNA repair. The breast cancer type 2 susceptibility protein interacts with the RAD51 protein, a key component in homologous recombination and double-strand break repair. Through this interaction, BRCA2 regulates the availability and activity of RAD51, which coats single–strand DNA to form a nucleoprotein filament that invades and pairs with a homologous DNA duplex to initiate strand exchange. BRCA2 is involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair, and is considered a tumor suppressor gene. Most BRCA2 pathogenic variants reported to date consist of frameshift deletions, insertions, or nonsense variants that predict premature truncation of protein transcription, consistent with the loss of function that is expected with clinically significant mutation of tumor suppressor genes. Cells lacking BRCA2 are deficient in the repair of double-strand DNA breaks, as reflected in a hypersensitivity to ionizing radiation.

Inherited BRCA2 pathogenic variants confer an increased lifetime risk of developing breast and ovarian cancer. In a study by Antoniou et al. (2003) based on 22 populations, the BRCA2–related risks for both, breast and ovarian cancer by age 70 were estimated to be 45% (95% CI = 33% to 54%) and 11% (95% CI = 4% to 18%), respectively. In another population-based study, the cumulative cancer risks for breast and ovarian cancer by age 70 in individuals with a germline BRCA2 pathogenic variant were r eported as 49% and 18%, respectively (Chen & Parmigiani, 2007). The contralateral breast cancer risk in BRCA2 heterozygotes is 12% within five years of the initial breast cancer diagnosis (Metcalfe et al., 2004). The relative risk for prostate cancer in males with a BRCA2 pathogenic variant is 4.6% (Breast Cancer Linkage Consortium, 1999). Although it is less well studied, the literature suggests that pancreatic cancer and melanoma risks may be elevated in families with a detected BRCA2 pathogenic variant (Breast Cancer Linkage Consortium, 1999; Hearle et al., 2003; van Asperen et al., 2005). Biallelic mutations in BRCA2 can cause Fanconi Anemia (FA-D1), characterized by congenital defects, bone marrow failure and chromosomal instability. [Load More]