What problem does it solve?
Clinical interpretation of structural variants (deletions, duplications, inversions, translocations) requires synthesizing gene content, dosage sensitivity, population frequency, and literature evidence into a defensible ACMG classification, which is slow and error-prone when done manually.
Core Features & Use Cases
- Seven-phase SV workflow: Normalizes coordinates, annotates gene content, assesses ClinGen HI/TS dosage sensitivity, checks gnomAD/ClinVar/DECIPHER frequencies, scores pathogenicity on a 0-10 scale, and applies ACMG-adapted evidence codes.
- Five-tier classification with explicit evidence: Produces Pathogenic/Likely Pathogenic/VUS/Likely Benign/Benign calls with per-criterion rationale (PVS1, PS1, PM2, PP4, BA1, etc.) and confidence grading.
- Structured clinical reports: Generates a standardized markdown report with executive summary, gene tables, scoring breakdown, clinical recommendations, and reproductive risk guidance.
- Use Case: Given a 283 kb deletion at chr17:31094927-31377677 in a patient with café-au-lait spots, the skill retrieves NF1 dosage sensitivity and ClinVar evidence, classifies the variant as Pathogenic, and outputs a full clinical report with surveillance recommendations.
Quick Start
Interpret the deletion at chr17:31094927-31377677 (GRCh38) in a patient with café-au-lait spots and neurofibromas, and generate a full ACMG classification report.
