NM_147127.5(EVC2):c.1855C>T (p.Gln619Ter) AND Ellis-van Creveld syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 5, 2022
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:: RCV000003551.8

Allele description [Variation Report for NM_147127.5(EVC2):c.1855C>T (p.Gln619Ter)]

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]

Observations:

Condition(s)

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

Recent activity

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NADH dehydrogenase subunit 6 (mitochondrion) [Eudiscopus denticulus]
NADH dehydrogenase subunit 6 (mitochondrion) [Eudiscopus denticulus]
gi|1958836346|gb|QQV68432.1|

Protein
ATP synthase F0 subunit 8 (mitochondrion) [Eudiscopus denticulus]
ATP synthase F0 subunit 8 (mitochondrion) [Eudiscopus denticulus]
gi|2088246987|ref|YP_010148066.1|

Protein
cytochrome c oxidase subunit III (mitochondrion) [Eudiscopus denticulus]
cytochrome c oxidase subunit III (mitochondrion) [Eudiscopus denticulus]
gi|2088246989|ref|YP_010148068.1|

Protein
Nontransport Unintentional Injuries - Injury Prevention and Environmental Health
Nontransport Unintentional Injuries - Injury Prevention and Environmental Health
EEG with generalized slow activity
EEG with generalized slow activity

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023709	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2003)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002061202	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 5, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12571802, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023709

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 2003)

germline

literature only

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

SCV002061202

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 5, 2022)

germline

clinical testing

PubMed (2)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome.

Ruiz-Perez VL, Tompson SW, Blair HJ, Espinoza-Valdez C, Lapunzina P, Silva EO, Hamel B, Gibbs JL, Young ID, Wright MJ, Goodship JA.

Am J Hum Genet. 2003 Mar;72(3):728-32. Epub 2003 Feb 4.

PubMed [citation]

PMID:: 12571802
PMCID:: PMC1180248

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 OMIM, SCV000023709.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an Ecuadorian family in which 2 daughters had Ellis-van Creveld syndrome (225500) , Ruiz-Perez et al. (2003) found an 1855C-T transition in exon 12 of the EVC2 gene creating a nonsense codon (gln619 to stop). Both had disproportionate short stature with acromesomelic limb shortening and short ribs. In the hands, there was postaxial polydactyly with nail dysplasia and fusion of the hamate and capitate. Both had oligodontia with dysplastic teeth and multiple oral frenula. One of the girls had genu valgum.

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

From DASA, SCV002061202.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The c.1855C>T;p.(Gln619*) variant creates a premature translational stop signal in the EVC2 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 3384; PMID: 12571802) - PS4. This variant is not present in population databases (rs137852925, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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