NM_147127.5(EVC2):c.942G>A (p.Trp314Ter) AND Ellis-van Creveld syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 6, 2017
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:: RCV000665893.7

Allele description [Variation Report for NM_147127.5(EVC2):c.942G>A (p.Trp314Ter)]

NM_147127.5(EVC2):c.942G>A (p.Trp314Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_147127.5(EVC2):c.942G>A (p.Trp314Ter)

HGVS:

NC_000004.12:g.5665578C>T
NG_015821.1:g.48971G>A
NM_001166136.2:c.702G>A
NM_147127.5:c.942G>AMANE SELECT
NP_001159608.1:p.Trp234Ter
NP_667338.3:p.Trp314Ter
NC_000004.11:g.5667305C>T
NM_147127.4:c.942G>A

Protein change:

W234*

Links:

dbSNP: rs763363403

NCBI 1000 Genomes Browser:

rs763363403

Molecular consequence:

NM_001166136.2:c.702G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_147127.5:c.942G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Ellis-van Creveld syndrome (EVC)
Synonyms:: MESOECTODERMAL DYSPLASIA; Chondroectodermal dysplasia
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
SCV000790089	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Mar 6, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV004048583	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000790089

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Mar 6, 2017)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV004048583

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel homozygous mutations in the EVC and EVC2 genes in two consanguineous families segregating autosomal recessive Ellis-van Creveld syndrome.

Aziz A, Raza SI, Ali S, Ahmad W.

Clin Dysmorphol. 2016 Jan;25(1):1-6. doi: 10.1097/MCD.0000000000000104.

PubMed [citation]

PMID:: 26580685

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Counsyl, SCV000790089.1

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

#	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 Neuberg Centre For Genomic Medicine, NCGM, SCV004048583.1

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

Description

The stop gained variant has been reported previously in homozygous state in a family affected with Ellis-van Creveld syndrome (Aziz A. et al., 2016). The p.Trp314Ter variant is reported with the allele frequency (0.0008%) in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar with varying interpretations: Pathogenic/ Likely Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. No significant reportable EVC2 variant was detected in the spouse.

#	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: Jan 13, 2025

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