ClinVar Genomic variation as it relates to human health
NM_001142800.2(EYS):c.9019G>T (p.Asp3007Tyr)
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.
Pathogenic(1); Likely pathogenic(3); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001142800.2(EYS):c.9019G>T (p.Asp3007Tyr)
Variation ID: 1500117 Accession: VCV001500117.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6q12 6: 63721012 (GRCh38) [ NCBI UCSC ] 6: 64430908 (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 Mar 28, 2022 Apr 20, 2024 Jan 7, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001142800.2:c.9019G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001136272.1:p.Asp3007Tyr missense NM_001370348.2:c.*7304C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NM_001290259.2:c.*7304C>A 3 prime UTR NM_001292009.2:c.9082G>T NP_001278938.1:p.Asp3028Tyr missense NM_001370349.2:c.*7304C>A 3 prime UTR NM_001370350.2:c.*7304C>A 3 prime UTR NM_015153.4:c.*7304C>A 3 prime UTR NC_000006.12:g.63721012C>A NC_000006.11:g.64430908C>A NG_023443.2:g.1991214G>T - Protein change
- D3028Y, D3007Y
- Other names
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- Canonical SPDI
- NC_000006.12:63721011:C: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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00003
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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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PHF3 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
127 | 674 | |
EYS | - | - |
GRCh38 GRCh37 |
4129 | 4683 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 7, 2024 | RCV002042503.6 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 13, 2023 | RCV002246649.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 9, 2022 | RCV002509739.1 |
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
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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
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 25
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002519626.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Likely pathogenic
(Dec 09, 2022)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002819395.1
First in ClinVar: Jan 15, 2023 Last updated: Jan 15, 2023 |
Comment:
Variant summary: EYS c.9019G>T (p.Asp3007Tyr) results in a non-conservative amino acid change located in the Laminin G domain of the encoded protein sequence. Three of … (more)
Variant summary: EYS c.9019G>T (p.Asp3007Tyr) results in a non-conservative amino acid change located in the Laminin G domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-06 in 156460 control chromosomes. c.9019G>T has been reported in the literature in individuals affected with Retinitis Pigmentosa. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Likely pathogenic
(Jun 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 25
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004195270.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Jan 02, 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: SCV002295774.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 3007 of the EYS protein … (more)
This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 3007 of the EYS protein (p.Asp3007Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with retinitis pigmentosa (PMID: 21179430, 29159838, 31814702; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as p.D3028Y. ClinVar contains an entry for this variant (Variation ID: 1500117). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EYS protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Uncertain Significance
(Jan 07, 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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004847416.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Asp3028Tyr variant in EYS has been reported in the homozygous state in at least 3 individuals with retinitis pigmentosa (Khan 2010 PMID: 21179430, Iwanami … (more)
The p.Asp3028Tyr variant in EYS has been reported in the homozygous state in at least 3 individuals with retinitis pigmentosa (Khan 2010 PMID: 21179430, Iwanami 2019 PMID: 31814702, Invitae pers. comm.). This variant segregated with EYS-associated disorder(s) in 1 affected relative from 1 family (Khan 2010 PMID: 21179430). This variant has been identified in 0.01% (4/41446) of African/African American chromosomes by gnomAD (http://gnomad.broadinstitute.org, v3.1.2). This variant has also been reported in ClinVar (Variation ID 1500117). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM3, PM2_Supporting, PP1. (less)
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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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Five major sequence variants and copy number variants in the EYS gene account for one-third of Japanese patients with autosomal recessive and simplex retinitis pigmentosa. | Iwanami M | Molecular vision | 2019 | PMID: 31814702 |
EYS mutation update: In silico assessment of 271 reported and 26 novel variants in patients with retinitis pigmentosa. | Messchaert M | Human mutation | 2018 | PMID: 29159838 |
Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa. | Khan MI | Molecular vision | 2010 | PMID: 21179430 |
Text-mined citations for rs888739369 ...
HelpRecord last updated May 01, 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.