CDH2

Chr 18ARAD

cadherin 2

Also known as: ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325, NCAD

NCBI Gene: 1000ENSG00000170558UniProt: P19022OMIM: 114020

This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone. [provided by RefSeq, Nov 2015]

OMIMResearchGenerating clinical summary…
LOFmechanismAR/ADLOEUF 0.293 OMIM phenotypes
Clinical Summary— CDH2
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Gene-Disease Validity (ClinGen)
arrhythmogenic right ventricular cardiomyopathy · ADLimited

Limited evidence — not for standalone diagnostic reporting

3 total gene-disease associations curated

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 609 VUS of 1160 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.29LOEUF
pLI 0.992
Z-score 5.05
OE 0.15 (0.08–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.09Z-score
OE missense 0.74 (0.68–0.81)
376 obs / 508.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.15 (0.08–0.29)
0≤0.351.4
Missense OE?0.74 (0.68–0.81)
0≤0.61.4
Synonymous OE?0.98
0≤1.21.6
LoF obs/exp: 6 / 40.8Missense obs/exp: 376 / 508.9Syn Z: 0.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCDH2-related arrhythmogenic right ventricular cardiomyopathyOTHERAD
strongCDH2-related syndromic neurodevelopmental disorder with corpus callosum, axon, cardiac, ocular, and genital defectsOTHERAD

This gene — mechanism propensity

DN
0.5082th %ile
GOF
0.6346th %ile
LOF
0.63top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation · 38% of P/LP variants are LoF · LOEUF 0.29

Literature Evidence

LOFCHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 24834135 ↗

ClinVar Variant Classifications

1160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic16
VUS609
Likely Benign435
Benign39
Conflicting30
8
Pathogenic
16
Likely Pathogenic
609
VUS
435
Likely Benign
39
Benign
30
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
6
0
0
8
Likely Pathogenic
7
8
1
0
16
VUS
33
547
24
5
609
Likely Benign
0
12
128
295
435
Benign
0
0
33
6
39
Conflicting
—30
Total425731863061,137

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

35 pathogenic / likely-pathogenic (of 46) ClinVar copy-number / structural variants overlap CDH2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CDH2 · 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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients