-
Notifications
You must be signed in to change notification settings - Fork 54
Description
The ClinGen SVI working group recommend using a points based system for calculating ACMG classifications
This is based on their earlier publication Modeling the ACMG/AMP variant classification gudielines as a Bayesian classification framework
Exomiser uses the recommendations for PP3/BP4 scaling based on the REVEL score detailed in Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria which crucially allow for BP4_Moderate which was not accounted for in the original ACMG/AMP recommendations. The authors mention:
A second approach would be to use the Tavtigian et al. framework,9 in either its initial iteration (see supplemental methods for suggested modifications), or in its simplified, points-based iteration,34 in which BP4_Moderate evidence would count as −2 points toward variant classification.
Given the changes in strengths from other recommendations e.g. PM2_Supporting (#502) and the required updates to combining rules, it is more robust to simply use the points-based approach and deprecate the other implementations for removal in the next major version.