Contribution of bioinformatics predictions and functional splicing assays to the interpretation of unclassified variants of the BRCA genes.

ABSTRACT: A large fraction of sequence variants of unknown significance (VUS) of the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 may induce splicing defects. We analyzed 53 VUSs of BRCA1 or BRCA2, detected in consecutive molecular screenings, by using five splicing prediction programs, and we classified them into two groups according to the strength of the predictions. In parallel, we tested them by using functional splicing assays. A total of 10 VUSs were predicted by two or more programs to induce a significant reduction of splice site strength or activation of cryptic splice sites or generation of new splice sites. Minigene-based splicing assays confirmed four of these predictions. Five additional VUSs, all at internal exon positions, were not predicted to induce alterations of

SUBMITTER: Thery JC 

PROVIDER: S-EPMC3190263 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature