This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ClinVar Genomic variation as it relates to human health
NM_001142800.2(EYS):c.5510G>C (p.Trp1837Ser)
Germline
Classification
Help
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.
(10)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(2); Likely benign(5)
Uncertain significance(1); Benign(2); Likely benign(5)
10
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001142800.2(EYS):c.5510G>C (p.Trp1837Ser)
Variation ID: 195937 Accession: VCV000195937.38
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 6q12 6: 64590357 (GRCh38) [ NCBI UCSC ] 6: 65300250 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jun 28, 2015 Aug 4, 2024 Jul 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001142800.2:c.5510G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001136272.1:p.Trp1837Ser missense NM_001292009.2:c.5510G>C NP_001278938.1:p.Trp1837Ser missense NC_000006.12:g.64590357C>G NC_000006.11:g.65300250C>G NG_023443.2:g.1121869G>C Q5T1H1:p.Trp1837Ser - Protein change
- W1837S
- Other names
- -
- Canonical SPDI
- NC_000006.12:64590356:C:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00100 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00078
1000 Genomes Project 0.00100
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00241
The Genome Aggregation Database (gnomAD) 0.00333
Trans-Omics for Precision Medicine (TOPMed) 0.00357
The Genome Aggregation Database (gnomAD), exomes 0.00399
Exome Aggregation Consortium (ExAC) 0.00486
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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| EYS | - | - |
GRCh38 GRCh37 |
4229 | 4790 | |
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. |
|---|---|---|---|---|
| Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 7, 2022 | RCV000176624.6 | |
| Uncertain significance (3) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV000504628.8 | |
| Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 9, 2020 | RCV000665978.11 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2024 | RCV000963176.21 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Nov 19, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000228312.5
First in ClinVar: Jun 28, 2015 Last updated: Jun 28, 2015 |
Number of individuals with the variant: 2
Sex: mixed
|
|
|
Uncertain significance
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000464418.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
|
|
|
Likely benign
(Mar 17, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 25
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000790202.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
|
|
|
Likely benign
(Apr 09, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 25
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001159163.2
First in ClinVar: Feb 10, 2020 Last updated: Jan 26, 2021 |
|
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001865806.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 24265693)
|
|
|
Likely benign
(Jun 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002555712.1
First in ClinVar: Aug 08, 2022 Last updated: Aug 08, 2022 |
Comment:
Variant summary: EYS c.5510G>C (p.Trp1837Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging … (more)
Variant summary: EYS c.5510G>C (p.Trp1837Ser) results in a non-conservative amino acid change in 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 0.004 in 153716 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 1.17 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 benign. c.5510G>C has been reported in the literature in individuals affected with Retinitis Pigmentosa, however it is often observed in the heterozygous state without a variant reported in the second allele and in several studies the variant was considered to be a polymorphism (example Audo_2010, Eisenberger_2013, Wang_2014, Perez-Carro_2016). These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. Six ClinVar submitters have provided assessments for this variant after 2014. Two classified the variant as benign, three as likely benign, and one as VUS. Based on the evidence outlined above, the variant was classified as likely benign. (less)
|
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001110313.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(Jul 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV003917074.11
First in ClinVar: Apr 23, 2023 Last updated: Aug 04, 2024 |
Comment:
EYS: BP4, BS2
Number of individuals with the variant: 4
|
|
|
Likely benign
(Jan 01, 2015)
|
no assertion criteria provided
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000599155.2
First in ClinVar: Sep 09, 2017 Last updated: Sep 21, 2018 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: European
|
|
|
Benign
(Jan 10, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001459613.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
Comment:
Comment:
This variant is associated with the following publications: (PMID: 24265693)
Comment:
Variant summary: EYS c.5510G>C (p.Trp1837Ser) results in a non-conservative amino acid change in 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 0.004 in 153716 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 1.17 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 benign. c.5510G>C has been reported in the literature in individuals affected with Retinitis Pigmentosa, however it is often observed in the heterozygous state without a variant reported in the second allele and in several studies the variant was considered to be a polymorphism (example Audo_2010, Eisenberger_2013, Wang_2014, Perez-Carro_2016). These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. Six ClinVar submitters have provided assessments for this variant after 2014. Two classified the variant as benign, three as likely benign, and one as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
Comment:
EYS: BP4, BS2
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. |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Comment:
This variant is associated with the following publications: (PMID: 24265693)
Comment:
Variant summary: EYS c.5510G>C (p.Trp1837Ser) results in a non-conservative amino acid change in 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 0.004 in 153716 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 1.17 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 benign. c.5510G>C has been reported in the literature in individuals affected with Retinitis Pigmentosa, however it is often observed in the heterozygous state without a variant reported in the second allele and in several studies the variant was considered to be a polymorphism (example Audo_2010, Eisenberger_2013, Wang_2014, Perez-Carro_2016). These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. Six ClinVar submitters have provided assessments for this variant after 2014. Two classified the variant as benign, three as likely benign, and one as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
Comment:
EYS: BP4, BS2
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa. | Perez-Carro R | Scientific reports | 2016 | PMID: 26806561 |
| Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa. | Wang J | Investigative ophthalmology & visual science | 2014 | PMID: 25097241 |
| Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies. | Eisenberger T | PloS one | 2013 | PMID: 24265693 |
| 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 |
| 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 rs199689193 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record 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.