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

The 2015 ACMG/AMP variant classification recommendations included pathogenic (PP1) and benign (BS4) criteria for co-segregation, but details for using them were sparse. We developed a points-based co-segregation heuristic and integrated the specific phenotype criterion (PP4). We also show that negative evidence at one locus constitutes positive evidence for other loci.

Source: The American Journal of Human Genetics - December 15, 2023 Category: Genetics & Stem Cells Authors: Leslie G. Biesecker, Alicia B. Byrne, Steven M. Harrison, Tina Pesaran, Alejandro A. Sch äffer, Brian H. Shirts, Sean V. Tavtigian, Heidi L. Rehm, ClinGen Sequence Variant Interpretation Working Group Tags: Article Source Type: research