Whole genome analysis and the search for mutations in germline and tumor DNAs is becoming a major tool in the evaluation of risk as well as the management of hereditary cancer syndromes. Because of the identification of cancer predisposition gene panels, thousands of such variants have been catalogued yet many remain unclassified, presenting a clinical challenge for the management of hereditary cancer syndromes. Although algorithms exist to estimate the likelihood of a variant being deleterious, these tools are rarely used for clinical decision-making. Here, we review the progress in classifying K3326X, a rare truncating variant on the C-terminus of BRCA2 and review recent literature on other novel single nucleotide polymorphisms, SNPs, on the C-terminus of the protein, defined in this review as the portion after the final BRC repeat (amino acids 2058-3418).
Keywords: BRCA2; HBOC; HBOPC; K33326X; hereditary breast and ovarian cancer syndrome; hereditary breast ovarian and pancreatic cancer syndrome.