In the study sample of Ashkenazi Jewish individuals, we did not identify common pathogenic mutations in the BRCA1/2 genes but found high-penetrance mutations in other cancer associated genes such as MSH6, APC and MSH2. Pathogenic variants in HBOC moderate-risk genes such as CHEK2 were frequent in study participants without personal history of cancer. The gene discussed is MSH2; the disease is cancer.