Functional Analysis of a Large set of BRCA2 exon 7 Variants Highlights the Predictive Value of Hexamer Scores in Detecting Alterations of Exonic Splicing Regulatory Elements

摘要: Exonic variants can alter pre-mRNA splicing either by changing splice sites or modifying regulatory elements. Often these effects are difficult to predict and only detected performing RNA analyses. Here, we analyzed, in a minigene assay, 26 identified the exon 7 of BRCA2, cancer predisposition gene. Our results revealed eight new exon skipping mutations this exon: one directly altering 5' site seven affecting potential This brings number BRCA2 total 11, remarkably high considering reported (n = 36), all tested our assay. We then exploited large set data test predictive value regulator hexamers' scores recently established Ke et al. (). Comparisons hexamer-based predictions with experimental sensitivity detecting that increased skipping, an important feature for prescreening before analysis. In conclusion, hexamer represent promising tool predicting biological consequences exonic may have applications interpretation high-throughput sequencing.