Possible pathogenic hits (see excel file): 1. BRCA2 c.8873_8874insAAGT 22): potential increase lifetime risk of breast cancer of 40-80% and ovarian cancer of 11-40% 2. BRCA2 c.1536delT I *11) / "likely pathogenic": potential increase lifetime risk of breast cancer of 40-80% and ovarian cancer of 11-40% In males, if confirmed, consider testing female family members and be aware of potential increased risk of prostate cancer. BRCA2 is a gene on 13q13.1 encoding a 10.4-kb transcript and composed of 27 exons. The gene product is a 380-kd protein made up of 3,418 amino acids. Like BRCA1, BRCA2 is a tumor suppressor gene whose mutations increased risk of breast, ovarian, and other cancers through loss of function. BRCA2 appears to be involved in the DNA repair process through protein interaction with the RAD51 protein, a key component in homologous recombination and double-strand break repair. Pathogenic BRCA1 or BRCA2 mutations cause hereditary breast and ovarian cancer syndrome (HBOC), and, to a lesser extent, also increase risk for other cancers such as prostate cancer, pancreatic cancer, and melanoma. The lifetime risk for these cancers in individuals with a mutation in BRCA1 or BRCA2 is estimated to be: The lifetime risk for these cancers in individuals with a mutation in BRCA1 or BRCA2 is estimated to be: • 40%-80% for breast cancer (vs a 12% baseline risk in the general population) • 11%-40% for ovarian cancer (vs a 1-2% baseline risk in the general population) • 1%-10% for male breast cancer (vs a 0.1% baseline risk in the general population) • Up to 38% for prostate cancer (vs a 15-18% baseline risk in the general population) • 1%-7% for pancreatic cancer (vs a 0.5% baseline risk in the general population) • Patients with BRCA2 mutations may also be at an increased risk for melanoma It is also well recognized that BRCA1 and BRCA2 mutations have incomplete penetrance and variable expressivity. So, there is wide variability in age of on