ClinVar Genomic variation as it relates to human health
NM_147127.5(EVC2):c.1195C>T (p.Arg399Ter)
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.1195C>T (p.Arg399Ter)
Variation ID: 3383 Accession: VCV000003383.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4p16.2 4: 5640789 (GRCh38) [ NCBI UCSC ] 4: 5642516 (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 Apr 21, 2017 Feb 28, 2024 Jan 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_147127.5:c.1195C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_667338.3:p.Arg399Ter nonsense NM_001166136.2:c.955C>T NP_001159608.1:p.Arg319Ter nonsense NC_000004.12:g.5640789G>A NC_000004.11:g.5642516G>A NG_015821.1:g.73760C>T - Protein change
- R399*, R319*
- Other names
- -
- Canonical SPDI
- NC_000004.12:5640788: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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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00005
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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 |
1829 | 2102 | |
LOC126806961 | - | - | - | GRCh38 | - | 177 |
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 (5) |
no assertion criteria provided
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Jun 1, 2017 | RCV000003550.11 | |
Pathogenic/Likely pathogenic (2) |
no assertion criteria provided
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Jun 1, 2017 | RCV000516144.4 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 22, 2021 | RCV000578498.8 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2024 | RCV000763528.11 |
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. |
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Pathogenic
(Oct 31, 2018)
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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: SCV000894340.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Jul 22, 2021)
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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: SCV000680767.2
First in ClinVar: Feb 13, 2018 Last updated: Feb 13, 2018 |
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 disease; This … (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: 33452237, 29068549, 21199751, 23276573, 12571802, 17024374, 23026208, 25525159) (less)
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Pathogenic
(Jan 25, 2018)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000859321.1
First in ClinVar: Feb 13, 2018 Last updated: Feb 13, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(May 22, 2021)
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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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AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002501386.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
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Pathogenic
(Jan 04, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000626058.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg399*) 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.Arg399*) 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 (rs137852924, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Ellis-van Creveld syndrome (PMID: 12571802, 21199751, 23026208). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3383). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 08, 2017)
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no assertion criteria provided
Method: clinical testing
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Ellis-van Creveld syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000791341.2
First in ClinVar: Dec 26, 2017 Last updated: Dec 23, 2019 |
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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: SCV001479600.1
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: SCV001479761.1
First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
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Pathogenic
(Mar 01, 2003)
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no assertion criteria provided
Method: literature only
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ELLIS-VAN CREVELD SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000023708.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 21, 2017 |
Comment on evidence:
In a stillborn child with Ellis-van Creveld syndrome (225500) who had ventricular septal defect and short limbs with postaxial polydactyly of the hands and radiographic … (more)
In a stillborn child with Ellis-van Creveld syndrome (225500) who had ventricular septal defect and short limbs with postaxial polydactyly of the hands and radiographic features typical of EVC, with short limbs and classic pelvic configuration, Ruiz-Perez et al. (2003) found an 1195C-T transition in exon 10 of the EVC2 gene that introduced a nonsense codon (arg399 to stop). (less)
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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:
unknown
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Dan Cohn Lab, University Of California Los Angeles
Accession: SCV000612085.1
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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Ellis-van Creveld Syndrome
Affected status: yes
Allele origin:
biparental
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Dan Cohn Lab, University Of California Los Angeles
Accession: SCV000612086.1
First in ClinVar: Dec 10, 2017 Last updated: Dec 10, 2017 |
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Pathogenic
(-)
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no assertion criteria provided
Method: literature only
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Ellis-van Creveld syndrome
Affected status: unknown
Allele origin:
paternal
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Prenatal Diagnosis Center, International Peace Maternity & Child Health Hospital
Accession: SCV004037445.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
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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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Ellis-Van Creveld Syndrome: Clinical and Molecular Analysis of 50 Individuals. | Aubert-Mucca M | Journal of medical genetics | 2023 | PMID: 35927022 |
Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies. | Zhang W | Human mutation | 2018 | PMID: 29068549 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
Identification of one novel mutation in the EVC2 gene in a Chinese family with Ellis-van Creveld syndrome. | Zhang Z | Gene | 2012 | PMID: 23026208 |
Two Adult Patients with Ellis-van Creveld Syndrome Extending the Clinical Spectrum. | Rudnik-Schöneborn S | Molecular syndromology | 2011 | PMID: 22190900 |
Ellis-van Creveld syndrome: prenatal diagnosis, molecular analysis and genetic counseling. | Chen CP | Taiwanese journal of obstetrics & gynecology | 2010 | PMID: 21199751 |
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 |
Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. | Ruiz-Perez VL | American journal of human genetics | 2003 | PMID: 12571802 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=EVC2 | - | - | - | - |
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Text-mined citations for rs137852924 ...
HelpRecord last updated Sep 29, 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.