Increasing the number of genes evaluated in individuals undergoing assessment for breast or ovarian cancer risk through large panels or whole exome sequencing (WES) does not increase the rate of molecular diagnosis, but rather, complicates reporting with a “substantial burden” of incidental and uncertain results, according to a study published May 5 in the American Journal of Human Genetics. The study also found clinical utility in the American College of Medical Genetics and Genomics (ACMG) variant-classification guidelines. The plummeting cost of sequencing and identification of an increasing number of potential breast-cancer-susceptibility variants have driven interest in the clinical use of large, multi-gene panels (sometimes with 100-plus genes) and WES to assess genetic cancer risk. However, the expanded sets of genes quarried have varying levels of evidence to support their association with cancer susceptibility and the large gene sets complicate results reporting because of incidental findings. Researchers from the SIMPLEXO (Simplifying Complex Exomes) consortium evaluated the ability of a variant-classification methodology based ACMG guidelines to define the rate of mutations and variants of uncertain significance (VUS) in 180 medically relevant genes in individuals who met guidelines for hereditary cancer risk evaluation. WES was performed in 404 individuals (from 253 families). The […]