tooluniverse-variant-analysis

When to Use This Skill

Triggers:

• User provides a VCF file (SNV/indel or SV) and asks questions about its contents
• Questions about variant allele frequency (VAF) filtering
• Mutation type classification queries (missense, nonsense, synonymous, etc.)
• Structural variant interpretation requests (deletions, duplications, CNVs)
• Variant annotation requests (ClinVar, gnomAD, CADD, dbSNP)
• CNV pathogenicity assessment using ClinGen dosage sensitivity
• Cohort comparison questions
• Population frequency filtering (SNVs or SVs)
• Intronic/intergenic variant filtering
• Gene dosage sensitivity queries

Example Questions:

• "What fraction of variants with VAF < 0.3 are annotated as missense mutations?"
• "After filtering intronic/intergenic variants, how many non-reference variants remain?"
• "What is the clinical significance of this deletion affecting BRCA1?"
• "Which dosage-sensitive genes overlap this 500kb duplication on chr17?"
• "How many variants have clinical significance annotations?"
• "Compare variant counts between samples"

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Core Capabilities

Capability	Description
VCF Parsing	Pure Python + cyvcf2 parsers. VCF 4.x, gzipped, multi-sample, SNV/indel/SV
Mutation Classification	Maps SO terms, SnpEff ANN, VEP CSQ, GATK Funcotator to standard types
VAF Extraction	Handles AF, AD, AO/RO, NR/NV, INFO AF formats
Filtering	VAF, depth, quality, PASS, variant type, mutation type, consequence, chromosome, SV size
Statistics	Ti/Tv ratio, per-sample VAF/depth stats, mutation type distribution, SV size distribution
Annotation	MyVariant.info (aggregates ClinVar, dbSNP, gnomAD, CADD, SIFT, PolyPhen)
SV/CNV Analysis	gnomAD SV population frequencies, DGVa/dbVar known SVs, ClinGen dosage sensitivity
Clinical Interpretation	ACMG/ClinGen CNV pathogenicity classification using haploinsufficiency/triplosensitivity scores
DataFrame	Convert to pandas for advanced analytics
Reporting	Markdown reports with tables and statistics, SV clinical reports

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