NM_147127.5(EVC2):c.142_151del (p.Asp49fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 23, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000704017.9

Allele description [Variation Report for NM_147127.5(EVC2):c.142_151del (p.Asp49fs)]

NM_147127.5(EVC2):c.142_151del (p.Asp49fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_147127.5(EVC2):c.142_151del (p.Asp49fs)

HGVS:

NC_000004.12:g.5708366_5708375del
NG_008843.1:g.2170_2179del
NG_015821.1:g.6177_6186del
NM_001166136.2:c.-13+457_-13+466del
NM_147127.5:c.142_151delMANE SELECT
NP_667338.3:p.Asp49fs
NC_000004.11:g.5710090_5710099del
NC_000004.11:g.5710093_5710102del
NM_147127.4:c.142_151del
NM_147127.4:c.142_151del10
NM_147127.4:c.142_151delCGGGATCCCC

Protein change:

D49fs

Links:

dbSNP: rs1221185345

NCBI 1000 Genomes Browser:

rs1221185345

Molecular consequence:

NM_147127.5:c.142_151del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001166136.2:c.-13+457_-13+466del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Ellis-van Creveld syndrome (EVC)
Synonyms:: MESOECTODERMAL DYSPLASIA; Chondroectodermal dysplasia
Identifiers:: MONDO: MONDO:0009162; MedGen: C0013903; Orphanet: 289; OMIM: 225500

Name:: Curry-Hall syndrome (WAD)
Synonyms:: WEYERS ACRODENTAL DYSOSTOSIS
Identifiers:: MONDO: MONDO:0008673; MedGen: C0457013; Orphanet: 952; OMIM: 193530

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000832950	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 23, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17024374, 19810119, 19876929, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000832950

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 23, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000832950.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant has not been reported in the literature in individuals with EVC2-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Asp49Trpfs*9) in the EVC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Jul 5, 2025

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