The BRCA2 gene, also known as the FANCD1 gene, was identified in 1995 on chromosome 13 as a breast and ovarian cancer risk gene (Wooster 1995; Chen 2006; Mavadatt 2013). Deleterious germline mutations in BRCA2 have been associated with an increased risk of pancreatic cancer (Iqbal 2012). Recent studies show that BRCA2 mutations may also be associated with an increased risk of metastatic prostate cancer (Kote-Jarai 2011; Gallagher 2010) and melanoma (Moran 2012).
Individuals with biallelic (homozygous or compound heterozygous) mutations in BRCA2 can present with Fanconi anemia, an autosomal recessive disorder characterized by physical abnormalities, bone marrow failure, and an increased risk for malignancy such as solid tumors (Howlett 2002).
Affected Phenotypes Included in Penetrance Model
Breast Cancer (male and female)
Note: For the likelihood ratio calculation in this model, prostate cancer and melanoma are not counted as affected.
Coding the Pedigree
Code affected individuals in column 5 of the Excel or plain text file used to build your pedigree.
- Code "2" (affected) for individuals with breast or ovarian cancer.
- For the likelihood ratio calculation in this model, pancreatic cancer, prostate cancer, and melanoma are not counted as affected.
- Code "1" (unaffected) for individuals who have not had those cancers. Individuals who have only had prostate cancer, pancreatic cancer, and/or melanoma should be coded as "1."
- Code "0" for individuals with uncertain or unknown affected status.
More information on formatting pedigrees can be found here.
Penetrance classes for BRCA2
Penetrance is gender-specific.
|Age Range||Homozygous Normal||Heterozygous||Homozygous Normal||Heterozygous|
- Wooster R, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995, 378:789. PMID: 8524414
- Chen S, et al. Characterization of BRCA1 and BRCA2 mutations in a large United States sample. J Clin Oncol. 2006, 24:863. PMID: 16484695
- Mavaddat, N, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 2013, 105:812. PMID: 23628597
- Iqbal J, et al. The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2012, 107:2005. PMID: 23099806
- Kote-Jarai Z, et al. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br J Cancer. 2011, 105:1230. PMID:21952622
- Gallagher DJ, et al. Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res. 2010, 16:2115. PMID: 20215531
- Moran A, et al. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer. 2012, 11:235. PMID: 22187320
- Howlett NG, et al. Biallelic inactivation of BRCA2 in Fanconi anemia. Science. 2002, 297:606. PMID: 12065746