ClinVar Genomic variation as it relates to human health
NM_206933.4(USH2A):c.949C>A (p.Arg317=)
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_206933.4(USH2A):c.949C>A (p.Arg317=)
Variation ID: 2358 Accession: VCV000002358.49
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q41 1: 216325499 (GRCh38) [ NCBI UCSC ] 1: 216498841 (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 Dec 6, 2016 Apr 15, 2024 Jan 8, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_206933.4:c.949C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_996816.3:p.Arg317= synonymous NM_007123.6:c.949C>A NP_009054.6:p.Arg317= synonymous NC_000001.11:g.216325499G>T NC_000001.10:g.216498841G>T NG_009497.2:g.102950C>A - Protein change
- Other names
- USH2A, 949C-A, ARG317ARG
- R317R
- Canonical SPDI
- NC_000001.11:216325498:G: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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
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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USH2A | - | - |
GRCh38 GRCh37 |
6918 | 8386 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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Nov 4, 2023 | RCV000002452.16 | |
Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Jan 8, 2024 | RCV000412796.33 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 19, 2012 | RCV000824799.5 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 4, 2023 | RCV000984234.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 9, 2020 | RCV001199595.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000763297.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 1, 2017 | RCV000627017.4 | |
Pathogenic (1) |
criteria provided, single submitter
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May 9, 2019 | RCV001075725.2 |
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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Usher syndrome type 2A
Retinitis pigmentosa 39
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893962.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Nov 19, 2012)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000065652.6
First in ClinVar: May 03, 2013 Last updated: Aug 26, 2019 |
Comment:
The p.Arg317Arg (NM_206933.2 c.949C>A) variant in USH2A has been reported in 9 i ndividuals with Usher syndrome (Pennings 2004, Seyedahmadi 2004, Cremers 2007, D reyer … (more)
The p.Arg317Arg (NM_206933.2 c.949C>A) variant in USH2A has been reported in 9 i ndividuals with Usher syndrome (Pennings 2004, Seyedahmadi 2004, Cremers 2007, D reyer 2008, Vache 2010, Bonnet 2011). A second variant in USH2A was found in tr ans in at least 3 of these individuals (Pennings 2004, Vache 2010, Bonnet 2011). This variant has also been reported in ClinVar (Variation ID#2358) as pathogeni c. mRNA studies show that this variant leads to abnormal splicing and a frameshi ft (Vache 2010). This variant has been identified in (8/126206) of European chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs111033272). Although this variant has been seen in the general pop ulation, its frequency is low enough to be consistent with a recessive carrier f requency. In summary, this variant meets criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner based upon functional evide nce and its occurrence in individuals with this disease. ACMG/AMP Criteria appli ed: PVS1, PM2, PM3, PP5. (less)
Number of individuals with the variant: 4
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Pathogenic
(Jan 09, 2020)
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criteria provided, single submitter
Method: research
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Usher syndrome type 2
Affected status: yes
Allele origin:
germline
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Molecular Genetics Laboratory, Institute for Ophthalmic Research
Accession: SCV001162766.1
First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020 |
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Pathogenic
(Sep 26, 2017)
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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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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448877.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 2A
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001369018.2
First in ClinVar: May 12, 2018 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic.
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Pathogenic
(Feb 05, 2020)
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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: SCV000490867.3
First in ClinVar: Jan 09, 2017 Last updated: Mar 04, 2023 |
Comment:
Non-canonical splice site variant demonstrated to result in loss-of-function (Vache et al., 2010); Not observed at a significant frequency in large population cohorts (Lek et … (more)
Non-canonical splice site variant demonstrated to result in loss-of-function (Vache et al., 2010); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27957503, 15043528, 15015129, 30904819, 20513143, 26927203, 24944099, 23891399, 28944237, 15241801, 15325563, 21569298, 18273898, 16963483, 25575603, 30609409) (less)
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Pathogenic
(Nov 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 39
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004182925.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Nov 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 2A
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV004182926.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Oct 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa 39
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004208204.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 08, 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: SCV001219336.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects codon 317 of the USH2A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid … (more)
This sequence change affects codon 317 of the USH2A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the USH2A protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs111033272, gnomAD 0.006%). This variant has been observed in individual(s) with Usher syndrome type IIa or nonsydromic retinitis pigmentosa (PMID: 15241801, 20513143, 21569298, 26927203). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2358). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 20513143). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 01, 2019)
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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: SCV001248865.20
First in ClinVar: May 09, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Jan 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Abnormal macular morphology
Blindness Retinal pigment epithelial atrophy Pigmentary retinopathy Rod-cone dystrophy
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000747720.1
First in ClinVar: May 12, 2018 Last updated: May 12, 2018 |
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Pathogenic
(Apr 01, 2016)
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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: SCV000339779.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(May 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: SCV001241353.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(Apr 01, 2004)
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no assertion criteria provided
Method: literature only
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USHER SYNDROME, TYPE IIA
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022610.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 14, 2018 |
Comment on evidence:
For discussion of the arg317-to-arg (R317R) mutation in the USH2A gene that was found in compound heterozygous state in patients with Usher syndrome type IIa … (more)
For discussion of the arg317-to-arg (R317R) mutation in the USH2A gene that was found in compound heterozygous state in patients with Usher syndrome type IIa (USH2A; 276901) by van Wijk et al. (2004), see 608400.0007. (less)
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Likely pathogenic
(Jan 24, 2019)
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no assertion criteria provided
Method: clinical testing
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Usher syndrome type 2A
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132312.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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Likely pathogenic
(Jan 24, 2019)
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no assertion criteria provided
Method: clinical testing
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Retinitis pigmentosa 39
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132313.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001922732.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001959112.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Jan 29, 2021)
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no assertion criteria provided
Method: clinical testing
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Usher syndrome type 2A
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002094005.1
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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An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients. | Bonnet C | European journal of human genetics : EJHG | 2016 | PMID: 27460420 |
Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa. | Pierrache LH | Ophthalmology | 2016 | PMID: 26927203 |
Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis. | Lenarduzzi S | Hearing research | 2015 | PMID: 25575603 |
Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots. | Baux D | Human mutation | 2014 | PMID: 24944099 |
Experience of targeted Usher exome sequencing as a clinical test. | Besnard T | Molecular genetics & genomic medicine | 2014 | PMID: 24498627 |
Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. | Bonnet C | Orphanet journal of rare diseases | 2011 | PMID: 21569298 |
Nasal epithelial cells are a reliable source to study splicing variants in Usher syndrome. | Vaché C | Human mutation | 2010 | PMID: 20513143 |
Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II. | Dreyer B | Human mutation | 2008 | PMID: 18273898 |
Development of a genotyping microarray for Usher syndrome. | Cremers FP | Journal of medical genetics | 2007 | PMID: 16963483 |
Comprehensive screening of the USH2A gene in Usher syndrome type II and non-syndromic recessive retinitis pigmentosa. | Seyedahmadi BJ | Experimental eye research | 2004 | PMID: 15325563 |
USH2A mutation analysis in 70 Dutch families with Usher syndrome type II. | Pennings RJ | Human mutation | 2004 | PMID: 15241801 |
Evaluation of visual impairment in Usher syndrome 1b and Usher syndrome 2a. | Pennings RJ | Acta ophthalmologica Scandinavica | 2004 | PMID: 15043528 |
Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II. | van Wijk E | American journal of human genetics | 2004 | PMID: 15015129 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=USH2A | - | - | - | - |
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Text-mined citations for rs111033272 ...
HelpRecord last updated Apr 15, 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.