NM_147127.5(EVC2):c.534dup (p.Glu179Ter) AND Ellis-van Creveld syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 28, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000674426.5

Allele description [Variation Report for NM_147127.5(EVC2):c.534dup (p.Glu179Ter)]

NM_147127.5(EVC2):c.534dup (p.Glu179Ter)

Gene:

EVC2:EvC ciliary complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_147127.5(EVC2):c.534dup (p.Glu179Ter)

HGVS:

NC_000004.12:g.5689329dup
NG_015821.1:g.25220dup
NM_001166136.2:c.294dup
NM_147127.5:c.534dupMANE SELECT
NP_001159608.1:p.Glu99Ter
NP_667338.3:p.Glu179Ter
NC_000004.11:g.5691055_5691056insA
NC_000004.11:g.5691056dup
NM_147127.4:c.534dupT
NM_147127.5:c.534dupTMANE SELECT

Protein change:

E179*

Links:

dbSNP: rs1553851462

Molecular consequence:

NM_001166136.2:c.294dup - nonsense - [Sequence Ontology: SO:0001587]
NM_147127.5:c.534dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Ellis-van Creveld syndrome (EVC)
Synonyms:: MESOECTODERMAL DYSPLASIA; Chondroectodermal dysplasia; EVC-Related Ellis-van Creveld Syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009162; MedGen: C0013903; Orphanet: 289; OMIM: 225500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000799762	Counsyl	no assertion criteria provided	Likely pathogenic (May 4, 2018)	unknown	clinical testing
SCV005381646	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 1, 2024)	germline	clinical testing	Citation Link,
SCV007519734	Variantyx, Inc.	criteria provided, single submitter (Variantyx Assertion Criteria 2022)	Pathogenic (Nov 28, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17024374, 19810119, 19876929 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000799762

Counsyl

no assertion criteria provided

Likely pathogenic
(May 4, 2018)

unknown

clinical testing

SCV005381646

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 1, 2024)

germline

clinical testing

Citation Link,

SCV007519734

Variantyx, Inc.

criteria provided, single submitter

(Variantyx Assertion Criteria 2022)

Pathogenic
(Nov 28, 2025)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients.

Tompson SW, Ruiz-Perez VL, Blair HJ, Barton S, Navarro V, Robson JL, Wright MJ, Goodship JA.

Hum Genet. 2007 Jan;120(5):663-70. Epub 2006 Sep 21.

PubMed [citation]

PMID:: 17024374

Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling.

Valencia M, Lapunzina P, Lim D, Zannolli R, Bartholdi D, Wollnik B, Al-Ajlouni O, Eid SS, Cox H, Buoni S, Hayek J, Martinez-Frias ML, Antonio PA, Temtamy S, Aglan M, Goodship JA, Ruiz-Perez VL.

Hum Mutat. 2009 Dec;30(12):1667-75. doi: 10.1002/humu.21117.

PubMed [citation]

PMID:: 19810119

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000799762.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005381646.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: EVC2 c.534dupT (p.Glu179X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251446 control chromosomes. To our knowledge, no occurrence of c.534dupT in individuals affected with EVC2-related conditions has been reported. ClinVar contains an entry for this variant (Variation ID: 558195). Based on the evidence outlined above, the variant was classified as pathogenic for autosomal recessive Ellis-van Creveld syndrome.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Variantyx, Inc., SCV007519734.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This is a frameshift variant in the EVC2 gene (OMIM: 607261). Pathogenic variants in this gene have been associated with autosomal recessive Ellis-van Creveld syndrome. The clinical symptoms reported for this individual are highly specific for autosomal recessive Ellis-van Creveld syndrome, which has a limited genetic etiology (PMID: 37903214) (PP4). This variant introduces a premature termination codon in exon 5 out of 22 and is expected to result in loss of function, which is a known disease mechanism for EVC2 in this disorder (PMID: 17024374, 19810119, 19876929) (PVS1). This variant is absent from control populations (https://gnomad.broadinstitute.org/) (PM2). Based on the current evidence, this variant is classified as pathogenic for autosomal recessive Ellis-van Creveld syndrome.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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