Genomic Variant Interpretation

Overview

This is a reasoning skill. It encodes the decision frameworks used in clinical variant interpretation so the agent can help a user classify a genomic variant correctly, justify each piece of evidence, and avoid common pitfalls. It does not run tools or generate code. It assumes the user has variant-level annotation (HGVS nomenclature, population frequency, in silico predictors, ClinVar records, literature) and wants help reasoning about what the variant means.

Two standards dominate:

• ACMG/AMP 2015 (Richards et al., Genet Med) for germline variants in Mendelian disease, with later ClinGen Sequence Variant Interpretation (SVI) refinements (e.g., PVS1 decision tree, PP3/BP4 quantitative calibration, PM2_Supporting).
• AMP/ASCO/CAP 2017 (Li et al., JMD) for somatic variants in cancer, organized by clinical actionability tier (I–IV), not pathogenicity.

Confusing these two is the single most common interpretation error. Pick the framework first, then apply it.

Usage

Invoke this skill when the user asks you to: