domains / families / science / clinical-interpretation
Classify variant clinical significance with the ACMG/AMP germline framework and its 2018-2025 ClinGen refinements (graded PVS1 decision tree, PM2 downgraded to Supporting, PP5/BP6 retired, calibrated PP3/BP4, Bayesian points), the AMP/ASCO/CAP somatic tiers and ClinGen oncogenicity system, ClinVar star-rating and gnomAD grpmax filtering-AF interpretation. Use when deciding germline-vs-somatic framework, applying current (not flat-2015) ACMG points, checking for a gene-specific VCEP specification, judging whether a ClinVar assertion or gnomAD frequency is usable evidence, calibrating a pathogenicity predictor, evaluating PVS1 on the MANE Select transcript, or building a VUS reanalysis loop. Not for functional annotation itself (see variant-calling/variant-annotation).
The two skills cover the same task but with materially different and non-overlapping depth. The first copy (OpenClaw) is a practical, command-line workflow focused on downloading ClinVar, using bcftools for filtering, and running InterVar, but it relies on the older, flat 2015 ACMG criteria. The second copy (GPTomics) is a conceptual and methodological guide that explicitly warns against the 2015 defaults, mandates the use of 2018-2025 ClinGen refinements (e.g., graded PVS1, PM2 downgrade, PP5/BP6 retirement), and distinguishes between germline and somatic frameworks. Because the first copy's core classification method is explicitly identified as obsolete by the second, and the second lacks the specific shell commands for data retrieval and filtering found in the first, neither is a complete reproduction of the other. Combining them is necessary to provide a workflow that is both executable and methodologically current.