DSG2
Chr 18ADARdesmoglein 2
Also known as: CDHF5, HDGC
This gene encodes desmoglein-2, a calcium-binding transmembrane glycoprotein that forms desmosomes mediating cell-cell adhesion in cardiac, epithelial, and other tissues. Mutations cause arrhythmogenic right ventricular dysplasia and dilated cardiomyopathy, presenting as cardiac arrhythmias and heart failure primarily affecting the myocardium. The condition follows both autosomal dominant and autosomal recessive inheritance patterns.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
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
500 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 | 11 | 0 | 18 | 0 | 29 |
Likely Pathogenic | 19 | 1 | 4 | 0 | 24 |
VUS | 10 | 269 | 19 | 3 | 301 |
Likely Benign | 0 | 6 | 33 | 89 | 128 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 6 | |||
| Total | 40 | 276 | 75 | 92 | 489 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DSG2 · 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
External Resources
Links to major genomics databases and tools