Neurological ciliopathies

Gene: EVC2

Comment on phenotypes: Phenotypes accessed in OMIM on 22nd September 2025

Created: 22 Sep 2025, 1:16 p.m. | Last Modified: 22 Sep 2025, 1:16 p.m.

Panel Version: 6.3

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, 10:58 a.m. | Last Modified: 29 Aug 2025, 10:58 a.m.

Panel Version: 6.1

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 all the 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, 10:57 a.m. | Last Modified: 29 Aug 2025, 10:57 a.m.

Panel Version: 6.1

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

Comment on list classification: Confirmed DD gene for Ellis-van Creveld syndrome, more than 3 cases/family reports and different variants reported, green on the Unexplained skeletal dysplasia Version 1.3 gene panel.

Created: 13 Dec 2016, 2:07 p.m.