EXT2 c.536+17C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
exostoses, multiple, type 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +17 | near-intronic (+17 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.32 | GERP -2 |
| Non-coding constraint | Z 3.19 | 1 kb window · o/e 0.78 · regional · uncalibrated |
| Overall | ||
| CADD | 0.877 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,990 alleles
Overall
6.22e-05%
1/1,608,824 alleles · very rare
exomes 1/1,456,484 · genomes 0/152,340 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- EXT2
- Coding
- c.536+17C>A
- MANE Select
- NM_207122
- dbSNP
- rs773843696
- Type
- single nucleotide variant
- Location
- chr11:44108265 (GRCh38)
- Gene constraint
- LOEUF 0.775 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.59 · 6 PDB
Disease context
exostoses, multiple, type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Multiple osteochondromas (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Childhood
- Prevalence
- >1 / 1000 (Specific population)
Similar variants
- EXT2 c.1079+1G>A Pathogenic ★★ same condition
- EXT2 c.1079+1G>T Pathogenic ★★ same condition
- EXT2 c.1173+1G>A Pathogenic ★★ same condition
- EXT2 c.1662+1G>C Likely pathogenic ★★ same condition
- EXT2 c.536+1G>A Pathogenic ★★ same condition
- EXT2 c.626+1G>A Pathogenic ★★ same condition
- EXT2 c.626+1G>C Pathogenic ★★ same condition
- EXT2 c.626+1G>T Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ext2-c-536-plus-17c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown