In This Issue
Classifying the Effects of BRCA1 and BRCA2 Variants on Splicing – A Systematic Study
Article first published online: 18 SEP 2013
© 2013 WILEY PERIODICALS, INC.
Volume 34, Issue 10, page v, October 2013
How to Cite
Greenblatt, M. (2013), Classifying the Effects of BRCA1 and BRCA2 Variants on Splicing – A Systematic Study. Hum. Mutat., 34: v. doi: 10.1002/humu.22197
- Issue published online: 18 SEP 2013
- Article first published online: 18 SEP 2013
In this issue, Walker and colleagues (Hum Mutat 34:1424–1431, 2013) report on the “Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatics and splicing assay data: Inter-reviewer variability and promotion of minimum reporting guidelines”. This important contribution addresses the practical implications of classifying genetic variants by applying splicing data to BRCA1 and BRCA2. The authors present the results of the ENIGMA Consortium's efforts to assess a previously published system for classifying variants that potentially alter splicing. The system assigns specific probabilities for pathogenicity to each class. Analysis of published data from multiple previous reports of BRCA1 and BRCA2 variants highlights the successes and weaknesses of current strategies, including how the rules work when good splicing data are available, inter-reviewer variability in interpretation, and the difficulty of getting good splicing data from which to apply the rules. They propose suggestions for minimum reporting guidelines for splicing assays, and improvements to the 5-tier splicing classification system to allow future evaluation of its performance as a clinical tool.