C2CD2
Chr 21C2 calcium dependent domain containing 2
Also known as: C21orf25, C21orf258, TMEM24L
C2CD2 encodes a protein that localizes to the cytosol and nucleus. Mutations cause autosomal recessive intellectual disability and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to reduced protein levels.
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
186 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 | 0 | 0 | 76 | 0 | 76 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 72 | 5 | 0 | 77 |
Likely Benign | 0 | 8 | 1 | 1 | 10 |
Benign | 0 | 0 | 1 | 4 | 5 |
Conflicting | — | 1 | |||
| Total | 0 | 80 | 85 | 5 | 171 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
C2CD2 · 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 →No open access results found
External Resources
Links to major genomics databases and tools