Blacklisting variants common in private cohorts but not in public databases optimizes human exome analysis.

ABSTRACT: Computational analyses of human patient exomes aim to filter out as many nonpathogenic genetic variants (NPVs) as possible, without removing the true disease-causing mutations. This involves comparing the patient's exome with public databases to remove reported variants inconsistent with disease prevalence, mode of inheritance, or clinical penetrance. However, variants frequent in a given exome cohort, but absent or rare in public databases, have also been reported and treated as NPVs, without rigorous exploration. We report the generation of a blacklist of variants frequent within an in-house cohort of 3,104 exomes. This blacklist did not remove known pathogenic mutations from the exomes of 129 patients and decreased the number of NPVs remaining in the 3,104 individual exomes by a median

SUBMITTER: Maffucci P 

PROVIDER: S-EPMC6338851 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature