Regional-specific calibration enables application of computational evidence for clinical classification of 5' cis-regulatory variants in Mendelian disease.

ABSTRACT: To date, clinical genetic testing for Mendelian disease variants has focused heavily on exonic coding and intronic gene regions. This multi-step study was undertaken to provide an evidence base for selecting and applying computational approaches for use in clinical classification of 5' cis-regulatory region variants. Curated datasets of clinically reported disease-causing 5' cis-regulatory region variants and variants from matched genomic regions in population controls were used to calibrate six bioinformatic tools as predictors of variant pathogenicity. Likelihood ratio estimates were aligned to code weights following ClinGen recommendations for application of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification scheme

SUBMITTER: Villani RM 

PROVIDER: S-EPMC11267523 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature