NM_147127.5(EVC2):c.1855C>T (p.Gln619Ter) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 26, 2023
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:: RCV001228211.9

Allele description

NM_147127.5(EVC2):c.1855C>T (p.Gln619Ter)

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.1855C>T (p.Gln619Ter)

HGVS:

NC_000004.12:g.5628590G>A
NG_015821.1:g.85959C>T
NM_001166136.2:c.1615C>T
NM_147127.5:c.1855C>TMANE SELECT
NP_001159608.1:p.Gln539Ter
NP_667338.3:p.Gln619Ter
NC_000004.11:g.5630317G>A
NM_147127.4:c.1855C>T

Protein change:

Q539*; GLN619TER

Links:

OMIM: 607261.0005; dbSNP: rs137852925

NCBI 1000 Genomes Browser:

rs137852925

Molecular consequence:

NM_001166136.2:c.1615C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_147127.5:c.1855C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Name:: Curry-Hall syndrome (WAD)
Synonyms:: Acrofacial dysostosis of Weyers; 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
SCV001400599	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 26, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17024374, 19810119, 19876929, 12571802, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001400599

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 26, 2023)

germline

clinical testing

PubMed (5)
[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 (5)

Details of each submission

From Invitae, SCV001400599.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Gln619*) 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). This variant is present in population databases (rs137852925, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with Ellis-van Creveld Syndrome (PMID: 12571802). ClinVar contains an entry for this variant (Variation ID: 3384). 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: Mar 5, 2024

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