ClinVar Genomic variation as it relates to human health
NM_001142800.2(EYS):c.8648_8655del (p.Thr2883fs)
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_001142800.2(EYS):c.8648_8655del (p.Thr2883fs)
Variation ID: 550019 Accession: VCV000550019.21
- Type and length
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Deletion, 8 bp
- Location
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Cytogenetic: 6q12 6: 63721376-63721383 (GRCh38) [ NCBI UCSC ] 6: 64431272-64431279 (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 Aug 5, 2018 Jun 17, 2024 Mar 6, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001142800.2:c.8648_8655del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001136272.1:p.Thr2883fs frameshift NM_001370348.2:c.*7669_*7676del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NM_001142800.1:c.8648_8655delCATGCAGA NM_001290259.2:c.*7669_*7676del 3 prime UTR NM_001292009.2:c.8711_8718del NP_001278938.1:p.Thr2904fs frameshift NM_001370349.2:c.*7669_*7676del 3 prime UTR NM_001370350.2:c.*7669_*7676del 3 prime UTR NM_015153.4:c.*7669_*7676del 3 prime UTR NC_000006.12:g.63721377_63721384del NC_000006.11:g.64431273_64431280del NG_023443.2:g.1990843_1990850del NG_034034.2:g.90577_90584del - Protein change
- T2883fs, T2904fs
- Other names
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- Canonical SPDI
- NC_000006.12:63721375:TCTGCATGT: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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- 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 |
149 | 703 | |
EYS | - | - |
GRCh38 GRCh37 |
4232 | 4793 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (7) |
criteria provided, multiple submitters, no conflicts
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Mar 6, 2024 | RCV000664636.12 | |
Pathogenic (2) |
criteria provided, single submitter
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Mar 24, 2023 | RCV000787599.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 1, 2023 | RCV000802397.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 9, 2019 | RCV001073669.3 |
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
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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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Likely pathogenic
(Dec 29, 2017)
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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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Counsyl
Accession: SCV000788634.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(Aug 09, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001239221.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(Apr 08, 2021)
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criteria provided, single submitter
Method: research
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Retinitis pigmentosa 25
Affected status: yes
Allele origin:
germline
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Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573433.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The EYS c.8648_8655del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The EYS c.8648_8655del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic. (less)
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Pathogenic
(Dec 01, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000942227.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Thr2883Lysfs*4) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Thr2883Lysfs*4) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 262 amino acid(s) of the EYS protein. This variant is present in population databases (rs528919874, gnomAD 0.6%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 20537394). It has also been observed to segregate with disease in related individuals. This variant is also known as c.8710_8717del8 (p.T2904KfsX4). ClinVar contains an entry for this variant (Variation ID: 550019). This variant disrupts a region of the EYS protein in which other variant(s) (p.Tyr2935*) have been determined to be pathogenic (PMID: 22363543). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 25
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002579229.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1_STR, PM3, PS4_SUP, PM2_SUP
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Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Oct 07, 2022)
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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: SCV001813684.3
First in ClinVar: Sep 08, 2021 Last updated: Mar 04, 2023 |
Comment:
Commonly seen in cis with the p.(C385*) variant in individuals of Finish background (Avela et al., 2018); Frameshift variant in the C-terminus predicted to result … (more)
Commonly seen in cis with the p.(C385*) variant in individuals of Finish background (Avela et al., 2018); Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 262 amino acids are lost and replaced with 3 incorrect amino acids; This variant is associated with the following publications: (PMID: 30718709, 20537394, 29159838, 28704921, 29550188, 31429209, 32531858, 29068140, 33833316) (less)
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Pathogenic
(Mar 24, 2023)
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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: SCV003922791.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
Variant summary: EYS c.8648_8655delCATGCAGA (p.Thr2883LysfsX4) is located in the last exon, and results in a premature termination codon that is not expected to cause nonsense … (more)
Variant summary: EYS c.8648_8655delCATGCAGA (p.Thr2883LysfsX4) is located in the last exon, and results in a premature termination codon that is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein, removing a part of the 3144 amino acids long protein. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 0.00075 in 157422 control chromosomes, predominantly at a frequency of 0.0064 within the Finnish subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency in the Finnish subpopulation is higher than the estimated maximal expected allele frequency for a pathogenic variant in EYS causing Retinitis Pigmentosa (0.0034). However, the Finnish subpopulation has been recently reported to be enriched for certain founder mutations in EYS (Avela_2018, Avela_2019). The presence of homozygotes in controls suggests that this variant may have incomplete penetrance and/or is associated with a later onset of disease. The variant, c.8648_8655delCATGCAGA, has been reported in the literature in multiple compound heterozygous and homozygous individuals affected with Retinitis Pigmentosa (e.g. Littink_2010, Westin_2021), and was also reported in cis with the c.1155T>A (p.Cys385X) variant in multiple Finish patients (Avela_2018, Avela_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as pathogenic (n = 7) or likely pathogenic (n = 2). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jun 22, 2023)
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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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Revvity Omics, Revvity
Accession: SCV004235273.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Pathogenic
(Mar 06, 2024)
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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: SCV004192871.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Apr 01, 2018)
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no assertion criteria provided
Method: research
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Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926582.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
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Pathogenic
(Jan 06, 2020)
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no assertion criteria provided
Method: curation
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Retinitis pigmentosa 25
Affected status: unknown
Allele origin:
germline
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Reproductive Health Research and Development, BGI Genomics
Accession: SCV001142361.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
Comment:
NM_001142800.1:c.8648_8655delCATGCAGA in the EYS gene has an allele frequency of 0.006 in European (Finnish) subpopulation in the gnomAD database. This sequence change results in a … (more)
NM_001142800.1:c.8648_8655delCATGCAGA in the EYS gene has an allele frequency of 0.006 in European (Finnish) subpopulation in the gnomAD database. This sequence change results in a premature translational stop signal in the EYS gene (p.Thr2883Lysfs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 262 amino acids of the EYS protein. This variant has been observed in a patient with retinitis pigmentosa, in a compound heterozygous state with c.4350_4356del7 (p.K1450KfsX3) (PMID: 20537394). This variant is also known as c.8710_8717del8 (p.T2904KfsX4) in the literature. Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PVS1; PM3; PP4. (less)
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Pathogenic
(Aug 23, 2021)
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no assertion criteria provided
Method: clinical testing
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Retinitis pigmentosa type 25
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002083481.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden. | Westin IM | Scientific reports | 2021 | PMID: 33833316 |
The genetic aetiology of retinal degeneration in children in Finland - new founder mutations identified. | Avela K | Acta ophthalmologica | 2019 | PMID: 31087526 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
A founder mutation in CERKL is a major cause of retinal dystrophy in Finland. | Avela K | Acta ophthalmologica | 2018 | PMID: 29068140 |
Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population. | Hosono K | PloS one | 2012 | PMID: 22363543 |
Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype. | Littink KW | Ophthalmology | 2010 | PMID: 20537394 |
Text-mined citations for rs528919874 ...
HelpRecord last updated Oct 13, 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.