ClinGen guidance for use of the PP1/BS4 co-segregation and PP4 phenotype specificity criteria for sequence variant pathogenicity classification.

ABSTRACT: The 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant classification publication established a standard employed internationally to guide laboratories in variant assessment. Those recommendations included both pathogenic (PP1) and benign (BS4) criteria for evaluating the inheritance patterns of variants, but details of how to apply those criteria at appropriate evidence levels were sparse. Several publications have since attempted to provide additional guidance, but anecdotally, this issue is still challenging. Additionally, it is not clear that those prior efforts fully distinguished disease-gene identification considerations from variant pathogenicity considerations nor did they address autosomal-recessive and X-linked inheritance.

SUBMITTER: Biesecker LG 

PROVIDER: S-EPMC10806742 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature