NM_153717.3(EVC):c.2T>C (p.Met1Thr) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 31, 2021
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:: RCV002954055.3

Allele description [Variation Report for NM_153717.3(EVC):c.2T>C (p.Met1Thr)]

NM_153717.3(EVC):c.2T>C (p.Met1Thr)

Genes:

LOC129992144:ATAC-STARR-seq lymphoblastoid silent region 15223 [Gene]
EVC:EvC ciliary complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_153717.3(EVC):c.2T>C (p.Met1Thr)

HGVS:

NC_000004.12:g.5711382T>C
NG_008843.1:g.5186T>C
NG_008843.2:g.5183T>C
NG_015821.1:g.3167A>G
NG_015821.2:g.3166A>G
NM_001306090.2:c.2T>C
NM_001306092.2:c.2T>C
NM_153717.3:c.2T>CMANE SELECT
NP_001293019.1:p.Met1Thr
NP_001293021.1:p.Met1Thr
NP_714928.1:p.Met1Thr
NC_000004.11:g.5713109T>C

Protein change:

M1T

Molecular consequence:

NM_001306090.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001306092.2:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_153717.3:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001306090.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001306092.2:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_153717.3:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003279788	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 31, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19810119, 28854412, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003279788

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 31, 2021)

germline

clinical testing

PubMed (3)
[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

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

Wide-spread cone-shaped epiphyses in two Saudi siblings with Ellis-van Creveld syndrome.

Al-Fardan A, Al-Qattan MM.

Int J Surg Case Rep. 2017;39:212-217. doi: 10.1016/j.ijscr.2017.08.022. Epub 2017 Aug 24.

PubMed [citation]

PMID:: 28854412
PMCID:: PMC5575438

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003279788.3

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

Description

This sequence change affects the initiator methionine of the EVC mRNA. The next in-frame methionine is located at codon 92. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Disruption of the initiator codon has been observed in individuals with Ellis-van Creveld syndrome (PMID: 19810119, 28854412). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency).

#	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: Sep 29, 2024

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