HMGA2
Chr 12ADhigh mobility group AT-hook 2
Also known as: BABL, HMGI-C, HMGIC, LIPO, SRS5, STQTL9
HMGA2 encodes a transcriptional regulator that controls cell cycle progression and positively regulates IGF2 expression. Mutations cause Silver-Russell syndrome 5, a growth disorder characterized by prenatal and postnatal growth restriction, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating intolerance to complete protein loss.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
74 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 | 0 | 16 | 0 | 21 |
Likely Pathogenic | 4 | 0 | 0 | 0 | 4 |
VUS | 4 | 14 | 5 | 0 | 23 |
Likely Benign | 1 | 1 | 5 | 4 | 11 |
Benign | 0 | 1 | 1 | 1 | 3 |
| Total | 14 | 16 | 27 | 5 | 62 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HMGA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools