Reevaluation of the BRCA2 truncating allele c.9976A >t (p.Lys3326Ter) in a familial breast cancer context

Abstract

The breast cancer predisposition gene, BRCA2, has a large number of genetic variants of unknown effect. The variant rs11571833, an A >T transversion in the final exon of the gene that leads to the creation of a stop codon 93 amino acids early (K3326∗), is reported as a neutral polymorphism but there is some evidence to suggest an association with an increased risk of breast cancer. We assessed whether this variant was enriched in a cohort of breast cancer cases ascertained through familial cancer clinics compared to population-based non-cancer controls using a targeted sequencing approach. We identified the variant in 66/2634 (2.5%) cases and 33/1996 (1.65%) controls, indicating an enrichmen..