EVC2

Chr 4ARAD

EvC ciliary complex subunit 2

Also known as: LBN, WAD

The protein is a component of the EvC complex that positively regulates ciliary Hedgehog signaling and plays a critical role in bone formation and skeletal development. Mutations cause Ellis-van Creveld syndrome (chondroectodermal dysplasia), an autosomal recessive skeletal dysplasia, and Weyers acrofacial dysostosis, which combines limb and facial abnormalities and follows autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive disease mechanism for the more severe phenotype.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Ellis-van Creveld syndromeMIM #225500
AR
Weyers acrofacial dysostosisMIM #193530
AD
0
Active trials
15
Pubs (1 yr)
6
P/LP submissions
0%
P/LP missense
1.06
LOEUF
LOF
Mechanism· G2P
Clinical SummaryEVC2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 75 VUS of 100 total submissions
📖
GeneReview available — EVC2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.000
Z-score 1.11
OE 0.86 (0.691.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.14Z-score
OE missense 1.23 (1.161.30)
847 obs / 688.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.691.06)
00.351.4
Missense OE1.23 (1.161.30)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 58 / 67.8Missense obs/exp: 847 / 688.8Syn Z: -3.69
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEVC2-related acrofacial dysostosis, Weyers typeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5869th %ile
GOF
0.6833th %ile
LOF
0.4135th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

100 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS75
Likely Benign18
Benign1
4
Pathogenic
2
Likely Pathogenic
75
VUS
18
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
3
0
4
Likely Pathogenic
1
0
1
0
2
VUS
1
69
3
2
75
Likely Benign
0
1
9
8
18
Benign
0
0
1
0
1
Total3701710100

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

View in ClinVar →

Protein Context — Lollipop Plot

EVC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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