CADD score has limited clinical validity for the identification of pathogenic variants in noncoding regions in a hereditary cancer panel.

ABSTRACT:

Purpose

Several in silico tools have been shown to have reasonable research sensitivity and specificity for classifying sequence variants in coding regions. The recently developed combined annotation-dependent depletion (CADD) method generates predictive scores for single-nucleotide variants (SNVs) in all areas of the genome, including noncoding regions. We sought for non-coding variants to determine the clinical validity of common CADD scores.

Methods

We evaluated 12,391 unique SNVs in 624 patient samples submitted for germ-line mutation testing in a cancer-related gene panel. Stratifying by genomic region, we compared the distributions of CADD scores of rare SNVs, SNVs common in our patient population, and the null distribution of all possible SNVs.

Results

The medi

SUBMITTER: Mather CA 

PROVIDER: S-EPMC5097698 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature