ClinVar Genomic variation as it relates to human health
NM_001142800.2(EYS):c.6119T>A (p.Val2040Asp)
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.
Uncertain significance(2); Benign(1); Likely benign(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001142800.2(EYS):c.6119T>A (p.Val2040Asp)
Variation ID: 137257 Accession: VCV000137257.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q12 6: 64307042 (GRCh38) [ NCBI UCSC ] 6: 65016935 (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 May 29, 2016 May 12, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001142800.2:c.6119T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001136272.1:p.Val2040Asp missense NM_001292009.2:c.6119T>A NP_001278938.1:p.Val2040Asp missense NC_000006.12:g.64307042A>T NC_000006.11:g.65016935A>T NG_023443.2:g.1405184T>A Q5T1H1:p.Val2040Asp FM209056.1:c.6119T>A - Protein change
- V2040D
- Other names
- p.V2040D:GTT>GAT
- Canonical SPDI
- NC_000006.12:64307041:A:T
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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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0.00100 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00094
1000 Genomes Project 0.00100
The Genome Aggregation Database (gnomAD) 0.00166
The Genome Aggregation Database (gnomAD), exomes 0.00171
Exome Aggregation Consortium (ExAC) 0.00194
Trans-Omics for Precision Medicine (TOPMed) 0.00232
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
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. |
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EYS | - | - |
GRCh38 GRCh37 |
4129 | 4683 |
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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Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Mar 15, 2023 | RCV000177451.8 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000882506.13 | |
Uncertain significance (2) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001003019.5 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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May 18, 2021 | RCV001292621.4 |
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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Benign
(Dec 16, 2011)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000168382.4
First in ClinVar: Jun 19, 2014 Last updated: May 29, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Uncertain significance
(Oct 11, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 25
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001481212.2 First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Likely benign
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 25
Affected status: no
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001652878.1
First in ClinVar: May 29, 2021 Last updated: May 29, 2021 |
Sex: mixed
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Likely benign
(Feb 01, 2024)
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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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Invitae
Accession: SCV001025747.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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Likely benign
(Jun 17, 2014)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000229310.5
First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001321379.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Likely benign
(Mar 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002500083.2
First in ClinVar: Apr 23, 2022 Last updated: May 13, 2023 |
Comment:
Variant summary: EYS c.6119T>A (p.Val2040Asp) results in a non-conservative amino acid change located in the first laminin G repeat domain (IPR001791) of the encoded protein … (more)
Variant summary: EYS c.6119T>A (p.Val2040Asp) results in a non-conservative amino acid change located in the first laminin G repeat domain (IPR001791) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 152886 control chromosomes, predominantly at a frequency of 0.0038 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 1.11 fold of the estimated maximal expected allele frequency for a pathogenic variant in EYS causing Retinitis Pigmentosa phenotype (0.0034), strongly suggesting that the variant is a benign polymorphism. c.6119T>A has been reported in the literature in individuals affected with Retinitis Pigmentosa (Audo_2010, Barragan_2010, Sharon_2020, Dinero_2020). These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five other ClinVar submitters have assessed the variant since 2014: two classified the variant as of uncertain significance, two as likely benign, and one as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Likely benign
(Jan 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004157477.5
First in ClinVar: Nov 20, 2023 Last updated: May 12, 2024 |
Comment:
EYS: BP4
Number of individuals with the variant: 4
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Likely pathogenic
(Jun 23, 2019)
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no assertion criteria provided
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
inherited
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Sharon lab, Hadassah-Hebrew University Medical Center
Accession: SCV001161074.1
First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020 |
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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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Comprehensive genomic diagnosis of inherited retinal and optical nerve disorders reveals hidden syndromes and personalized therapeutic options. | Diñeiro M | Acta ophthalmologica | 2020 | PMID: 32483926 |
A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC). | Sharon D | Human mutation | 2020 | PMID: 31456290 |
PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly. | Zaki MS | Human mutation | 2016 | PMID: 26593283 |
Mutation spectrum of EYS in Spanish patients with autosomal recessive retinitis pigmentosa. | Barragán I | Human mutation | 2010 | PMID: 21069908 |
EYS is a major gene for rod-cone dystrophies in France. | Audo I | Human mutation | 2010 | PMID: 20333770 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=EYS | - | - | - | - |
Text-mined citations for rs201580493 ...
HelpRecord last updated May 12, 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.