NM_147127.5(EVC2):c.2239_2243del (p.Ala747fs) AND Ellis-van Creveld syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 20, 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:: RCV004771673.1

Allele description [Variation Report for NM_147127.5(EVC2):c.2239_2243del (p.Ala747fs)]

NM_147127.5(EVC2):c.2239_2243del (p.Ala747fs)

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.2239_2243del (p.Ala747fs)

HGVS:

NC_000004.12:g.5622795_5622799del
NG_015821.1:g.91750_91754del
NG_015821.2:g.91749_91753del
NM_001166136.2:c.1999_2003del
NM_147127.5:c.2239_2243delMANE SELECT
NP_001159608.1:p.Ala667fs
NP_667338.3:p.Ala747fs
NC_000004.11:g.5624522_5624526del

Protein change:

A667fs

Molecular consequence:

NM_001166136.2:c.1999_2003del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_147127.5:c.2239_2243del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Human sample from Homo sapiens
Human sample from Homo sapiens

biosample
Caenorhabditis elegans NR LBD domain-containing protein (nhr-21), mRNA
Caenorhabditis elegans NR LBD domain-containing protein (nhr-21), mRNA
gi|1845972396|ref|NM_001026930.4|

Nucleotide
Cichlasoma pearsei bio-material Chiapas microphthalmia-related transcription fac...
Cichlasoma pearsei bio-material Chiapas microphthalmia-related transcription factor b (Mitfb) gene, partial cds
gi|298353621|gb|GU946408.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005382343	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 20, 2023)	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

SCV005382343

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 20, 2023)

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

Citations

PubMed

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 Neuberg Centre For Genomic Medicine, NCGM, SCV005382343.1

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

Description

The frameshift variant c.2239_2243del (p.Ala747ArgfsTer65) in the EVC2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is absent in the gnomAD Exomes. This variant causes a frameshift starting with codon Alanine 747, changes this amino acid to Arginine residue, and creates a premature Stop codon at position 65 of the new reading frame. This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease causing (Vona et al., 2017). For these reasons, this variant has been classified as Likely 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		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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