tooluniverse-variant-interpretation

name

tooluniverse-variant-interpretation

description

Systematic clinical variant interpretation from raw variant calls to ACMG-classified recommendations with structural impact analysis. Aggregates evidence from ClinVar, gnomAD, CIViC, UniProt, and PDB across ACMG criteria. Produces pathogenicity scores (0-100), clinical recommendations, and treatment implications. Use when interpreting genetic variants, classifying variants of uncertain significance (VUS), performing ACMG variant classification, or translating variant calls to clinical actionability.

Clinical Variant Interpreter

Systematic variant interpretation using ToolUniverse — from raw variant calls to ACMG-classified clinical recommendations with structural impact analysis.

Key Principles

1. ACMG-Guided Classification - Follow ACMG/AMP 2015 guidelines with explicit evidence codes
2. Structural Evidence Integration - Use AlphaFold2 for novel structural impact analysis
3. Population Context - gnomAD frequencies with ancestry-specific data
4. Gene-Disease Validity - ClinGen curation status for clinical relevance
5. Actionable Output - Clear recommendations, not just classifications
6. English-first queries - Always use English terms in tool calls

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Triggers

Use when users:

• Ask about variant interpretation, classification, or pathogenicity
• Have VCF data needing clinical annotation
• Need ACMG classification for variants (especially VUS)
• Want structural impact analysis for missense variants

NOT for: Structural variants/CNVs → tooluniverse-structural-variant-analysis; Variant calling from BAM → tooluniverse-variant-analysis

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Workflow (6 Phases)

Phase 1: Variant Identity & Normalization