query-clinvar - SKILL.md Agent Skill

name: query-clinvar description: Query ClinVar for clinical variant significance. Use when user asks about variant pathogenicity, genetic variants, clinical significance, or disease-causing mutations. Triggers on "clinvar", "pathogenic", "variant significance", "clinical significance", "disease variant", "mutation pathogenicity".

ClinVar Clinical Variant Database

Query NCBI ClinVar for clinical significance of genetic variants.

When to Use

User asks if a variant is pathogenic
User wants to find known pathogenic variants in a gene
User asks about clinical significance of SNPs
User wants variant-disease associations

How to Execute

from Bio import Entrez
import json

Entrez.email = "molclaw@example.com"

# 1. Search ClinVar
def search_clinvar(query, max_results=10):
    handle = Entrez.esearch(db="clinvar", term=query, retmax=max_results)
    record = Entrez.read(handle)
    handle.close()
    return record

# 2. Fetch variant details
def fetch_clinvar(id_list):
    ids = ",".join(str(i) for i in id_list)
    handle = Entrez.efetch(db="clinvar", id=ids, rettype="vcv", retmode="xml")
    result = handle.read()
    handle.close()
    return result

# 3. Summary for ClinVar IDs
def clinvar_summary(id_list):
    ids = ",".join(str(i) for i in id_list)
    handle = Entrez.esummary(db="clinvar", id=ids, retmode="json")
    result = json.loads(handle.read())
    handle.close()
    return result

# Example: Find pathogenic BRCA1 variants
search = search_clinvar("BRCA1[gene] AND clinsig_pathogenic[prop]", max_results=5)
print(f"Total pathogenic BRCA1 variants: {search['Count']}")

if search['IdList']:
    summaries = clinvar_summary(search['IdList'])
    for uid in search['IdList']:
        info = summaries['result'].get(str(uid), {})
        title = info.get('title', 'N/A')
        clinical_sig = info.get('clinical_significance', {}).get('description', 'N/A')
        genes = info.get('genes', [{}])
        gene = genes[0].get('symbol', 'N/A') if genes else 'N/A'
        print(f"\nVariant: {title}")
        print(f"Gene: {gene}")
        print(f"Clinical significance: {clinical_sig}")

Common Search Patterns

Pathogenic variants in gene: BRCA1[gene] AND clinsig_pathogenic[prop]
By rsID: rs6025[rsid]
By disease: "breast cancer"[dis] AND clinsig_pathogenic[prop]
By chromosome region: 17[chr] AND 43000000:44000000[chrpos37]
Germline variants: BRCA1[gene] AND origin_germline[prop]

Clinical Significance Categories

Pathogenic, Likely pathogenic, Uncertain significance, Likely benign, Benign

Follow-up Suggestions

"Want me to check the allele frequency in gnomAD?"
"Should I look up this variant in Ensembl for more context?"
"Want me to find all pathogenic variants in this gene?"