Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines.

ABSTRACT:

Background

The American College of Medical Genetics and American College of Pathologists (ACMG/AMP) variant classification guidelines for clinical reporting are widely used in diagnostic laboratories for variant interpretation. The ACMG/AMP guidelines recommend complete concordance of predictions among all in silico algorithms used without specifying the number or types of algorithms. The subjective nature of this recommendation contributes to discordance of variant classification among clinical laboratories and prevents definitive classification of variants.

Results

Using 14,819 benign or pathogenic missense variants from the ClinVar database, we compared performance of 25 algorithms across datasets differing in distinct biological and technical variables. There was wide va

SUBMITTER: Ghosh R 

PROVIDER: S-EPMC5704597 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature