SkillHub

genomics

v1.0.0

Interpret genomic variants with ACMG classification, pharmacogenomics, and clinical annotation from ClinVar and gnomAD.

Sourced from ClawHub, Authored by Iván

Installation

Please help me install the skill `genomics` from SkillHub official store. npx skills add ivangdavila/genomics

Setup

On first use, read setup.md for integration guidelines. Ask user consent before creating ~/genomics/ workspace.

When to Use

User has processed genomic data (VCF files) and needs clinical interpretation. Agent handles variant classification, pharmacogenomics recommendations, and annotation lookup. NOT for raw data processing — use bioinformatics skill for alignment and variant calling.

Architecture

Memory lives in ~/genomics/. See memory-template.md for structure.

~/genomics/
├── memory.md           # Context + preferences + interpretation history
└── cases/              # Active interpretation cases

Quick Reference

Topic File
Setup process setup.md
Memory template memory-template.md

Core Rules

1. Classify Variants Using ACMG Guidelines

Every variant needs systematic classification:

Category Criteria
Pathogenic PVS1, PS1-4, PM1-6, PP1-5 weighted
Likely Pathogenic Strong + moderate evidence
VUS Insufficient or conflicting evidence
Likely Benign BS1-4, BP1-7 weighted
Benign Strong benign evidence

Never classify without evidence. State "insufficient data" when appropriate.

2. Check Population Frequency First

Before clinical interpretation, verify frequency:

Source Use For
gnomAD v4 Global population frequency
gnomAD non-cancer Somatic analysis
Population-specific Ancestry-appropriate filtering

MAF >1% in any population = likely benign for rare disease.

3. Cross-Reference Multiple Databases

Database Information
ClinVar Clinical classifications + submitter evidence
OMIM Gene-disease relationships
HGMD Literature-reported mutations
UniProt Protein function + domains

Single-source interpretation is insufficient. Triangulate evidence.

4. Report Pharmacogenomics Actionably

For drug-gene interactions, provide: - Diplotype (e.g., CYP2D6 1/4) - Predicted phenotype (poor/intermediate/normal/ultra-rapid metabolizer) - Drug list affected - Dosing guidance (CPIC/DPWG when available)

5. Separate Germline from Somatic Context

Context Key Differences
Germline Family implications, carrier testing, predictive
Somatic Tumor-specific, therapy selection, no inheritance

Always state which context you're interpreting.

6. Acknowledge Uncertainty

  • Novel variants often lack evidence
  • VUS ≠ benign — requires ongoing monitoring
  • Reclassification happens (ClinVar updates monthly)
  • Computational predictions are supportive, not definitive

Pharmacogenomics Reference

High-Priority Drug-Gene Pairs (CPIC Level A)

Gene Drugs Clinical Action
CYP2D6 Codeine, tramadol, tamoxifen, SSRIs Dosing/alternative
CYP2C19 Clopidogrel, PPIs, voriconazole Dosing/alternative
CYP2C9 + VKORC1 Warfarin Dosing algorithm
DPYD Fluorouracil, capecitabine Dose reduction/avoid
TPMT + NUDT15 Azathioprine, mercaptopurine Dose reduction
HLA-B*57:01 Abacavir Contraindication
HLA-B*15:02 Carbamazepine Contraindication (Asian ancestry)
SLCO1B1 Simvastatin Dose cap/alternative statin
G6PD Rasburicase, primaquine Contraindication
CYP3A5 Tacrolimus Dosing adjustment

Phenotype Interpretation

Metabolizer Status Meaning Typical Action
Poor (PM) Little/no enzyme activity Alternative drug or dose ↓↓
Intermediate (IM) Reduced activity Consider dose ↓
Normal (NM) Expected activity Standard dosing
Rapid/Ultra-rapid (UM) Increased activity Dose ↑ or alternative

Annotation Resources

Resource URL Content
ClinVar ncbi.nlm.nih.gov/clinvar Clinical variant classifications
gnomAD gnomad.broadinstitute.org Population frequencies
OMIM omim.org Gene-disease relationships
PharmGKB pharmgkb.org Drug-gene annotations
CPIC cpicpgx.org Pharmacogenomics guidelines
ClinGen clinicalgenome.org Gene-disease validity
Franklin franklin.genoox.com Variant interpretation aid
VarSome varsome.com ACMG auto-classification

Common Interpretation Traps

  • Ignoring population specificity — Variants common in African populations may look rare in European-biased databases
  • Trusting single ClinVar submitter — Check submitter count and review status (≥2 submitters, no conflict preferred)
  • Conflating computational prediction with evidence — CADD/REVEL are supportive, not diagnostic
  • Missing compound heterozygosity — Two VUS in trans can be pathogenic together
  • Outdated database versions — gnomAD v4 has 800K+ exomes vs v2's 125K
  • Ignoring gene-level constraint — pLI/LOEUF scores indicate tolerance to loss-of-function

External Endpoints

This skill does NOT automatically call external APIs. All database references are for manual lookup:

Resource When Used Data Sent
ClinVar, gnomAD, OMIM User manually visits None by this skill
PharmGKB, CPIC User manually visits None by this skill
VarSome, Franklin User manually visits None by this skill

No automatic network requests. The skill provides URLs and guidance for manual lookup only.

Security & Privacy

Data that stays local: - All interpretation work runs locally - No variant data sent externally by this skill - No automatic API calls to any database

This skill does NOT: - Make network requests automatically - Upload patient variants anywhere - Connect to databases without explicit user action - Store identifiable genomic information outside ~/genomics/

Install with clawhub install <slug> if user confirms: - medicine — clinical decision support - biology — molecular mechanisms - chemistry — drug metabolism pathways - health — patient care context

Feedback

  • If useful: clawhub star genomics
  • Stay updated: clawhub sync