Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1.

ABSTRACT:

Background

Germline variants affecting the proofreading activity of polymerases epsilon and delta cause a hereditary cancer and adenomatous polyposis syndrome characterized by tumors with a high mutational burden and a specific mutational spectrum. In addition to the implementation of multiple pieces of evidence for the classification of gene variants, POLE and POLD1 variant classification is particularly challenging given that non-disruptive variants affecting the proofreading activity of the corresponding polymerase are the ones associated with cancer. In response to an evident need in the field, we have developed gene-specific variant classification recommendations, based on the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology) crit

SUBMITTER: Mur P 

PROVIDER: S-EPMC10580551 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature