ClinVar Genomic variation as it relates to human health
NM_147127.5(EVC2):c.1708C>T (p.Gln570Ter)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_147127.5(EVC2):c.1708C>T (p.Gln570Ter)
Variation ID: 446664 Accession: VCV000446664.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4p16.2 4: 5631795 (GRCh38) [ NCBI UCSC ] 4: 5633522 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Dec 10, 2017 Feb 28, 2024 Dec 25, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_147127.5:c.1708C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_667338.3:p.Gln570Ter nonsense NM_001166136.2:c.1468C>T NP_001159608.1:p.Gln490Ter nonsense NC_000004.12:g.5631795G>A NC_000004.11:g.5633522G>A NG_015821.1:g.82754C>T - Protein change
- Q570*, Q490*
- Other names
- -
- Canonical SPDI
- NC_000004.12:5631794:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00003
The Genome Aggregation Database (gnomAD) 0.00005
Trans-Omics for Precision Medicine (TOPMed) 0.00005
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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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. |
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EVC2 | - | - |
GRCh38 GRCh37 |
1815 | 2078 |
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. |
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Pathogenic/Likely pathogenic (2) |
no assertion criteria provided
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Jun 1, 2017 | RCV000515819.3 | |
Pathogenic/Likely pathogenic (2) |
no assertion criteria provided
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Jun 1, 2017 | RCV000516102.3 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 21, 2017 | RCV000666197.5 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 25, 2023 | RCV001245243.7 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 5, 2023 | RCV001574376.9 |
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
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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. |
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Pathogenic
(Mar 21, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ellis-van Creveld syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000790449.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(Jan 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Curry-Hall syndrome
Ellis-van Creveld syndrome
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002811666.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001801187.2
First in ClinVar: Aug 21, 2021 Last updated: Feb 18, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 17024374, 34313030, 19876929, 29068549) (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Ellis-van Creveld syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Lifecell International Pvt. Ltd
Accession: SCV003924054.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
A Homozygote, Nonsense variant c.1708C>T in Exon 11 of the EVC2 gene that results in the amino acid substitution p.Gln570* was identified. The observed variant … (more)
A Homozygote, Nonsense variant c.1708C>T in Exon 11 of the EVC2 gene that results in the amino acid substitution p.Gln570* was identified. The observed variant has a maximum allele frequency of 0.00003/0.00003% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (Clinvar ID: 446664). This disorder has previously been reported in the patient affected skeletal ciliopathies (Zhang W et. al 2017) Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines. (less)
Ethnicity/Population group: Asian
Geographic origin: India
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Pathogenic
(Dec 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022227.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Curry-Hall syndrome
Ellis-van Creveld syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001418516.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln570*) in the EVC2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln570*) in the EVC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). This variant is present in population databases (rs769864196, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with Ellis–van Creveld syndrome or short-rib polydactyly syndromes (PMID: 17024374, 19876929, 29068549). ClinVar contains an entry for this variant (Variation ID: 446664). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 01, 2017)
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no assertion criteria provided
Method: research
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Ellis-van Creveld Syndrome
Affected status: yes
Allele origin:
maternal
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Dan Cohn Lab, University Of California Los Angeles
Accession: SCV000612087.1
First in ClinVar: Dec 10, 2017 Last updated: Dec 10, 2017 |
Observation 1: Observation 2: |
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Pathogenic
(Jun 01, 2017)
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no assertion criteria provided
Method: research
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Short-rib thoracic dysplasia 6 with or without polydactyly
Affected status: yes
Allele origin:
maternal
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Dan Cohn Lab, University Of California Los Angeles
Accession: SCV000612091.1
First in ClinVar: Dec 10, 2017 Last updated: Dec 10, 2017 |
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Pathogenic
(Jun 01, 2017)
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no assertion criteria provided
Method: research
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Type IV short rib polydactyly syndrome
Affected status: yes
Allele origin:
unknown
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Dan Cohn Lab, University Of California Los Angeles
Accession: SCV000612119.1
First in ClinVar: Dec 10, 2017 Last updated: Dec 10, 2017 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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short-rib polydactyly syndrome type IV
Affected status: yes
Allele origin:
inherited
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University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001479699.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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short-rib polydactyly syndrome type II
Affected status: yes
Allele origin:
inherited
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University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001479750.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: research
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Ellis van Creveld syndrome
Affected status: yes
Allele origin:
inherited
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University of Washington Center for Mendelian Genomics, University of Washington
Accession: SCV001479928.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies. | Zhang W | Human mutation | 2018 | PMID: 29068549 |
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 |
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 rs769864196 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.