A Validated Functional Analysis of Partner and Localizer of BRCA2 Missense Variants for Use in Clinical Variant Interpretation.

ABSTRACT: Clinical genetic testing readily detects germline genetic variants. Yet, the rarity of individual variants limits the evidence available for variant classification, leading to many variants of uncertain significance (VUS). VUS cannot guide clinical decisions, complicating counseling and management. In hereditary breast cancer gene PALB2, approximately 50% of clinically identified germline variants are VUS and approximately 90% of VUS are missense. Truncating PALB2 variants have homologous recombination (HR) defects and rely on error-prone nonhomologous end-joining for DNA damage repair (DDR). Recent reports show that some missense PALB2 variants may also be damaging, but most functional studies have lacked benchmarking controls required for sufficient predictive power for clinical use. Her

SUBMITTER: Brnich SE 

PROVIDER: S-EPMC8491091 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature