K3326* mutation in breast cancer

Abstract

After more than 25 years since its identification in 1995, the mutational faults in the BRCA2 gene is recognized and accepted as a high-penetrance predisposition gene for breast cancer. Besides a large number of pathogenic mutations, there are thousands of VUS (variants of uncertain significance) described, with many of them localized on C-terminus. K3326* is a rare truncating variant on the C-terminus of BRCA2, which is reported in the literature, including ClinVar and Varsome database, as a neutral polymorphism. However, there is some evidence that suggests an elevated risk of breast cancer associated with K3326* variant. We present the case of a K3326* mutation carrier, affected patient aged 42 diagnosed with co-existing breast and ovarian cancer, suggesting that the variant is not neutral for breast and ovarian cancer risk. K3326 may need to be included in SNP panels and further investigated for breast cancer risk estimation.