VCV001073308.2 - ClinVar

NC_000004.11:g.(?_2200251)_(5710240_?)del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000004.11:g.(?_2200251)_(5710240_?)del

Variation ID: 1073308 Accession: VCV001073308.2

Type and length

Deletion, 3,509,990 bp

Location

Cytogenetic: 4p16.3-16.2 4: 2200251-5710240 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	May 10, 2021	May 10, 2021	Jul 17, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NC_000004.11:g.(?_2200251)_(5710240_?)del

Protein change

Other names

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MSX1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	91	236
ADD1		-	-	GRCh38 GRCh37	54	185
ADRA2C		-	-	GRCh38 GRCh37	53	162
CYTL1		-	-	GRCh38 GRCh37	13	117
DOK7		-	-	GRCh38 GRCh37	1114	1347
EVC2		-	-	GRCh38 GRCh37	1881	2159
FAM193A		-	-	GRCh38 GRCh37	84	213
GRK4		-	-	GRCh38 GRCh37	48	186
HAUS3		-	-	GRCh38 GRCh37	-	188
HGFAC		-	-	GRCh38 GRCh37	98	222

There are 20 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Curry-Hall syndrome Ellis-van Creveld syndrome	Pathogenic (1)	criteria provided, single submitter	Jul 17, 2020	RCV001386270.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jul 17, 2020)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Curry-Hall syndrome Ellis-van Creveld syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001586434.1 First in ClinVar: May 10, 2021 Last updated: May 10, 2021	Publications: PubMed (5) PubMed: 25174843‚ 18454448‚ 17024374‚ 19810119‚ 19876929 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the EVC2 gene has been identified. The boundaries of this event are … (more) A gross deletion of the genomic region encompassing the full coding sequence of the EVC2 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of EVC2 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 25174843, 18454448). Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the EVC2 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of EVC2 have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 25174843, 18454448). Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Role of CGH array in the diagnosis of autosomal recessive disease: a case of Ellis-van Creveld syndrome.	D'Ambrosio V	Prenatal diagnosis	2015	PMID: 25174843
Ellis-van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands.	Ruiz-Perez VL	American journal of medical genetics. Part C, Seminars in medical genetics	2009	PMID: 19876929
Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling.	Valencia M	Human mutation	2009	PMID: 19810119
Long interspersed nuclear element-1 (LINE1)-mediated deletion of EVC, EVC2, C4orf6, and STK32B in Ellis-van Creveld syndrome with borderline intelligence.	Temtamy SA	Human mutation	2008	PMID: 18454448
Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients.	Tompson SW	Human genetics	2007	PMID: 17024374

Text-mined citations for this variant ...

Record last updated Jan 13, 2025

ClinVar Genomic variation as it relates to human health

NC_000004.11:g.(?_2200251)_(5710240_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...