---
name: genomics
slug: genomics
version: 1.0.0
description: Interpret genomic variants with ACMG classification, pharmacogenomics, and clinical annotation from ClinVar and gnomAD.
homepage: https://clawic.com/skills/genomics
metadata:
  clawdbot:
    emoji: 🧬
    requires:
      bins: []
    os:
    - linux
    - darwin
    - win32
    displayName: Genomics
---

## Setup

On first use, read `setup.md` for integration guidelines. Ask user consent before creating `~/Clawic/data/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 `~/Clawic/data/genomics/`. See `memory-template.md` for structure.

```
~/Clawic/data/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 ~/Clawic/data/genomics/

## Related Skills
More Clawic skills, get them at https://clawic.com/skills/<slug> (install if the user confirms):
- `medicine` — clinical decision support
- `biology` — molecular mechanisms
- `chemistry` — drug metabolism pathways
- `health` — patient care context

## Feedback

- If useful, star it: https://clawic.com/skills/genomics
- Latest version: https://clawic.com/skills/genomics


---
Source attribution: clawic
Original project: https://github.com/clawic/skills/blob/f825206afbf1c697202533a9187be68c7b697e0e/skills/genomics/SKILL.md
License: MIT
License information: https://opensource.org/license/mit
Original upstream instructions; downloaded from Mega AI Hub.

## Upstream license notice

MIT License

Copyright (c) 2026 Ivan G. Davila

Permission is hereby granted, free of charge, to any person obtaining a copy
of this software and associated documentation files (the "Software"), to deal
in the Software without restriction, including without limitation the rights
to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
copies of the Software, and to permit persons to whom the Software is
furnished to do so, subject to the following conditions:

The above copyright notice and this permission notice shall be included in all
copies or substantial portions of the Software.

THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
SOFTWARE.



# Mega AI Hub resource metadata

Creator / publisher: clawic
Original project: https://github.com/clawic/skills/blob/f825206afbf1c697202533a9187be68c7b697e0e/skills/genomics/SKILL.md
Attribution basis: Source repository record

Fields of work: Education & Research, Healthcare & Life Sciences
Roles: Clinical Research, Health Informatics, Medical Writer, Researcher
Specialties: Specialty not specified
Tools: Clinvar, Gnomad
Country applicability: Country not specified
Classification basis: Source catalog labels
Instruction SHA-256: 3ed0cde7dbb54cd4fc6f1d287f431428e7a78c2dcccc375371f0a6e3f1e54655