Reduced penetrance of pathogenic ACMG variants in a deeply phenotyped cohort study and evaluation of ClinVar classification over time.

ABSTRACT:

Purpose

We studied the penetrance of pathogenically classified variants in an elderly Dutch population from the Rotterdam Study, for which deep phenotyping is available. We screened the 59 actionable genes for which reporting of known pathogenic variants was recommended by the American College of Medical Genetics and Genomics (ACMG), and demonstrate that determining what constitutes a known pathogenic variant can be quite challenging.

Methods

We defined "known pathogenic" as classified pathogenic by both ClinVar and the Human Gene Mutation Database (HGMD). In 2628 individuals, we performed exome sequencing and identified known pathogenic variants. We investigated the clinical records of carriers and evaluated clinical events during 25 years of follow-up for evidence of varia

SUBMITTER: van Rooij J 

PROVIDER: S-EPMC7605437 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature