Expanding ACMG variant classification guidelines into a general framework.

ABSTRACT:

Background

The American College of Medical Genetics and Genomics (ACMG)-recommended five variant classification categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign) have been widely used in medical genetics. However, these guidelines are fundamentally constrained in practice owing to their focus upon Mendelian disease genes and their dichotomous classification of variants as being either causal or not. Herein, we attempt to expand the ACMG guidelines into a general variant classification framework that takes into account not only the continuum of clinical phenotypes, but also the continuum of the variants' genetic effects, and the different pathological roles of the implicated genes.

Main body

As a disease model, we employed chronic p

SUBMITTER: Masson E 

PROVIDER: S-EPMC9380380 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature