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tooluniverse-rare-disease-genomics

Investigate rare disease genetics from disease identification through variant interpretation using Orphanet, GenCC, and ClinVar.

1.7k|254|Updated Mar 3, 2025
Search Tags:#genomics#variant interpretation#clinvar#rare disease#orphanet#gencc#hpo phenotypes
One-click install
npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-rare-disease-genomics
Or copy as Structured Prompt for Agent▼
Please help me install this Agent Skill.
Skill: tooluniverse-rare-disease-genomics
Source: https://github.com/mims-harvard/ToolUniverse/tree/main/plugins/tooluniverse/skills/tooluniverse-rare-disease-genomics
Command: npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-rare-disease-genomics

SYSTEM DOCUMENTATION & REQUIREMENTS

What problem does it solve?

Rare disease research requires navigating fragmented databases (Orphanet, GenCC, ClinVar, HPO) with subtle parameter conventions and evidence hierarchies; this Skill orchestrates the full phenotype-to-variant investigation workflow so researchers avoid misclassified genes, misread VUS results, and wrong disease subtypes.

Core Features & Use Cases

  • Disease-to-Variant Pipeline: Resolves disease names to ORPHA codes, maps HPO phenotypes with frequency weights, identifies causative genes with association types, and validates gene-disease links via GenCC consensus classifications.
  • Variant Prioritization Logic: Applies inheritance-pattern filtering, allele frequency thresholds, consequence hierarchies, and ClinVar review-star confidence to narrow thousands of variants to causal candidates.
  • Translational Context: Pulls epidemiology, clinical trials, metabolite-disease links for inborn errors of metabolism, and literature evidence, then grades findings into Tier 1-4 confidence levels.
  • Use Case: Given a patient with suspected Marfan syndrome, resolve ORPHAcode 558, confirm FBN1 as a Definitive GenCC association, list expert-reviewed pathogenic ClinVar variants, and report prevalence plus recruiting clinical trials.

Quick Start

Ask the agent to investigate the genetic cause of a rare disease, for example: "Find the causative genes, pathogenic variants, and clinical trials for Marfan syndrome."

Frequently Asked Questions about tooluniverse-rare-disease-genomics

High-intent search queries and answers about installing and using this skill.

FAQPage Schema
How do I find the genetic cause of a rare disease?▼

Resolve the disease name to an ORPHA code with Orphanet_search_diseases, then call Orphanet_get_genes for causative genes and validate each with GenCC_search_disease. Check association types carefully, since candidate genes are not confirmed causes.

How to prioritize pathogenic variants in a candidate gene?▼

Filter by inheritance pattern first, then allele frequency (under 0.001 for dominant diseases), then consequence type with loss-of-function ranked highest. Confirm with ClinVar_search_variants using gene plus condition, and check review status stars for confidence.

What is the difference between ClinVar, GenCC, and Orphanet?▼

ClinVar answers whether a specific variant is pathogenic, GenCC answers whether a gene is validly linked to a disease with consensus classifications, and Orphanet provides disease definitions, phenotypes, and epidemiology. Check gene validity before interpreting variants.

Can a ClinVar VUS be reported as disease-causing?▼

No. A Variant of Uncertain Significance means evidence is insufficient to classify pathogenicity. The Skill explicitly prohibits reporting VUS as pathogenic and instead grades such findings as Tier 3 moderate evidence requiring further validation.

When should I not use this rare disease genomics workflow?▼

Avoid it for common diseases like type 2 diabetes, cancer variant interpretation, GWAS-based analysis, or pharmacogenomics, which have dedicated skills. Orphanet coverage is limited to rare diseases, so common conditions yield minimal entries.

Why does Orphanet search return the wrong disease subtype?▼

Disease names often map to subtypes or umbrella syndromes, so the first result may not be the exact condition. Always verify the ORPHA code matches the specific disease, for example Marfan syndrome is ORPHA 558, not the umbrella entry 284993.

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