GDF2
Chr 10ADgrowth differentiation factor 2
Also known as: BMP-9, BMP9, HHT5
The encoded protein is a secreted TGF-beta superfamily ligand that acts as a potent inhibitor of angiogenesis and regulates cartilage and bone development through SMAD1 signaling in endothelial cells. Mutations cause hereditary hemorrhagic telangiectasia type 5, inherited in an autosomal dominant pattern. This gene shows low constraint against loss-of-function variants, suggesting tolerance to protein loss.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
460 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 5 | 1 | 42 | 0 | 48 |
Likely Pathogenic | 0 | 3 | 17 | 0 | 20 |
VUS | 1 | 87 | 31 | 1 | 120 |
Likely Benign | 0 | 13 | 16 | 172 | 201 |
Benign | 0 | 1 | 45 | 1 | 47 |
Conflicting | — | 23 | |||
| Total | 6 | 105 | 151 | 174 | 459 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GDF2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools