Genomic Variant Interpretation

Interpret genomic variants by querying ClinVar, gnomAD, COSMIC, and other curated genomic databases. This skill provides ACMG/AMP-aligned pathogenicity classification, population frequency analysis, clinical significance assessment, and actionability evaluation for germline and somatic variants identified through clinical genomic testing.

Quick Install

npx skills add Open-Medica/open-medical-skills --skill genomics-variant-interpreter

What It Does

• ACMG/AMP classification framework: Applies the American College of Medical Genetics and Genomics (ACMG) / Association for Molecular Pathology (AMP) five-tier classification system (Pathogenic, Likely Pathogenic, Variant of Uncertain Significance, Likely Benign, Benign) with documented supporting criteria codes (PVS1, PS1-4, PM1-6, PP1-5, BA1, BS1-4, BP1-7)
• Multi-database cross-referencing: Queries ClinVar for curated pathogenicity assertions and review status, gnomAD for population allele frequencies across diverse ancestries, COSMIC for somatic mutation frequency in cancer types, and OMIM for gene-disease associations
• Population frequency analysis: Compares variant allele frequency across gnomAD populations (African, East Asian, European, Latino, South Asian) to identify ancestry-specific considerations and assess rarity using BA1 and BS1 frequency thresholds
• Somatic variant annotation: For tumor-derived variants, provides COSMIC prevalence data, known driver/passenger classification, associated cancer types, and tier-level evidence for therapeutic relevance using the AMP/ASCO/CAP somatic variant classification system
• Clinical actionability assessment: Links pathogenic/likely pathogenic variants to ClinGen-curated gene-disease validity classifications and actionability scores, identifying which findings warrant clinical intervention, surveillance, or cascade family testing

Clinical Use Cases