Functional characterization of all <i>CDKN2A</i> missense variants and comparison to in silico models of pathogenicity.

ABSTRACT: Interpretation of variants identified during genetic testing is a significant clinical challenge. In this study, we developed a high-throughput CDKN2A functional assay and characterized all possible CDKN2A missense variants. We found that 17.7% of all missense variants were functionally deleterious. We also used our functional classifications to assess the performance of in silico models that predict the effect of variants, including recently reported models based on machine learning. Notably, we found that all in silico models performed similarly when compared to our functional classifications with accuracies of 39.5-85.4%. Furthermore, while we found that functionally deleterious variants were enriched within ankyrin repeats, we did not identify any residues where all missense var

SUBMITTER: Kimura H 

PROVIDER: S-EPMC10793438 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature