Evaluating the impact of in silico predictors on clinical variant classification.

ABSTRACT:

Purpose

According to the American College of Medical Genetics and Genomics/Association of Medical Pathology (ACMG/AMP) guidelines, in silico evidence is applied at the supporting strength level for pathogenic (PP3) and benign (BP4) evidence. Although PP3 is commonly used, less is known about the effect of these criteria on variant classification outcomes.

Methods

A total of 727 missense variants curated by Clinical Genome Resource expert groups were analyzed to determine how often PP3 and BP4 were applied and their impact on variant classification. The ACMG/AMP categorical system of variant classification was compared with a quantitative point-based system. The pathogenicity likelihood ratios of REVEL, VEST, FATHMM, and MPC were calibrated using a gold standard set of 237 pa

SUBMITTER: Wilcox EH 

PROVIDER: S-EPMC9164215 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature