NC_000004.11:g.(?_5458281)_(5586509_?)del AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 7, 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:: RCV004580739.2

Allele description [Variation Report for NC_000004.11:g.(?_5458281)_(5586509_?)del]

NC_000004.11:g.(?_5458281)_(5586509_?)del

Genes:: EVC2:EvC ciliary complex subunit 2 [Gene - OMIM - HGNC]
LINC01587:long intergenic non-protein coding RNA 1587 [Gene - HGNC]
STK32B:serine/threonine kinase 32B [Gene - HGNC]
Variant type:: Deletion
Cytogenetic location:: 4p16.2
Genomic location:: Chr4: 5458281 - 5586509 (on Assembly GRCh37)
Preferred name:: NC_000004.11:g.(?_5458281)_(5586509_?)del
HGVS:: NC_000004.11:g.(?_5458281)_(5586509_?)del
This HGVS expression did not pass validation

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
SCV005064763	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 7, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12571802, 19810119, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005064763

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 7, 2023)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005064763.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the EVC2 protein in which other variant(s) (p.Ser1220Argfs*3) have been determined to be pathogenic (PMID: 12571802, 19810119). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with EVC2-related conditions. This variant results in the deletion of exons 18-22 and part of exon 17 (c.2898_*106294del) of the EVC2 gene. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product.

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

Last Updated: Sep 29, 2024

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