VarSome’s implementation of ACMG guidelines consists of two major steps:
- Automated scoring on each of the 18 rules.
- Manual review and adjustment on specific criteria to arrive at a final interpretation.
During the first step, VarSome's proprietary database consisting of more than 30 different databases serves to obtain necessary annotation information on variants for interpretation of pathogenicity of a given genomic variant. By doing so, VarSome gathers and presents all relevant evidence for subsequent manual review. Automated scoring is based on default parameters and users are advised to examine detailed evidence and use prior knowledge on ethnicity and/or disease to perform manual adjustments. In certain cases, we have taken into consideration expert opinions from VarSome’s Scientific Advisory Board and VarSome’s global community.
During the second step, the user can manually adjust each of the criteria on the basis of prior information (such as a variant’s de novo status) or his or her own domain knowledge to reach a final interpretation.