Skeletal dysplasia

Gene: EVC2

Green List (high evidence)

Comment on mode of inheritance: There are at least five unrelated families reported in literature with Weyers acrofacial dysostosis (rare skeletal dysplasia) and heterozygous variants in exon 22 of EVC2. While biallelic variants in EVC2 are associated with Ellis-van Creveld syndrome, Weyers acrofacial dysostosis is dominantly inherited. MOI should be changed from BIALLELIC to BOTH monoallelic and biallelic in the next GMS panel update.

Created: 29 Aug 2025, 10:36 a.m. | Last Modified: 29 Aug 2025, 10:52 a.m.

Panel Version: 8.6

Biallelic variants in EVC2 are associated with Ellis-van Creveld syndrome, characterised by short limbs, short ribs, postaxial polydactyly, and dysplastic nails and teeth.

Monoallelic variants have been reported in at least 5 families with Weyers acrofacial dysostosis (PMID:38531627;19810119;16404586). Affected individuals showed postaxial polydactyly in 1-4 limbs, 2-3 toe syndactyly, dysplastic nails, and abnormal dental presentation. All reported variants are in the last exon (22) of EVC2: c.3793delC, p.(Leu1265fs); c.3797T>A, p.(Leu1266Ter); c.3797T>G, p.(Leu1266Ter); c.3751G>T, p.(Glu1251Ter).

PMID: 23220543 D’Asdia et al., 2013 - 2 families with Weyers acrofacial dysostosis. EVC and EVC2 genes were screened and heterozygous mutations in the last exon of EVC2 were identified. ABSTRACT ONLY ACCESSED.

There is good evidence of dominant segregation of disease with the variant in the reported families. Thus, MOI should be changed from BIALLELIC to BOTH monoallelic and biallelic in the next GMS panel update.
This gene is associated with Autosomal Dominant Weyers acrofacial dysostosis, OMIM:193530 (accessed 26th Aug 2025).

Created: 29 Aug 2025, 10:35 a.m. | Last Modified: 29 Aug 2025, 10:35 a.m.

Panel Version: 8.6

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Weyers acrofacial dysostosis, OMIM:193530; acrofacial dysostosis, Weyers type, MONDO:0008673

Publications

• 38531627
• 23220543
• 19810119
• 16404586

Green List (high evidence)

Cilliopathies with major skeletal involvement gp of SDs, Dysostoses with predominant craniofacial involvement gp of SD. Variants in Weyers are dominant and cluster in exon 22, whereas variants in EVC are recessive. Many cases.; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ellis-van Creveld syndrome 225500; Weyers acrofacial dysostosis 193530

I don't know

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 11:31 p.m. | Last Modified: 11 Mar 2026, 11:31 p.m.

Panel Version: 8.37

Comment on phenotypes: Phenotypes accessed from OMIM 22nd September 2025.

Created: 22 Sep 2025, 1:02 p.m. | Last Modified: 22 Sep 2025, 1:02 p.m.

Panel Version: 8.12

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: EVC2; Initial rating suggestion: green

Created: 6 Mar 2019, 11:36 a.m.

Green List (high evidence)

Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve Abbs

Created: 27 Jul 2016, 9:34 a.m.

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:03 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Ellis-van Creveld syndrome 225500; Weyers acrofacial dysostosis 193530

Variants in this GENE are reported as part of current diagnostic practice