Large-scale application of ClinGen-InSiGHT APC-specific ACMG/AMP variant classification criteria leads to substantial reduction in VUS.

ABSTRACT: Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUSs), APC-specific variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) based on the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). A streamlined algorithm using the APC-specific criteria was developed and applied to assess all APC variants in ClinVar and the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) international reference APC Leiden Open

SUBMITTER: Yin X 

PROVIDER: S-EPMC11568752 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature