Interpretation of genomic variation and disease association: the great missense mutation challenge!
To the Editor,
The recent report from Downs et al. (April 2, 2015) illustrates the enormous challenge faced by researchers who are trying to identify germline genetic variants associated with breast cancer risk from the vast array of human genetic variation that is identified via whole exome capture and massively parallel sequencing (or similar). We are concerned that the current report lacks adequate attention to the detail required for genomic data filtering and interpretation in a study of this nature and has led to the overstatement that the two reported missense variants in PALB2, namely c.2014G>C p.E672Q and c.2993G>A p.G998E, are associated with breast cancer risk.
KeywordsBreast Cancer Breast Cancer Risk Missense Mutation BRCA1 Mutation Carrier Missense Variant
- 4.http://enigmaconsortium.org. Accessed 16 April 2015