ClinVar Genomic variation as it relates to human health
NM_206933.4(USH2A):c.2209C>T (p.Arg737Ter)
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.2209C>T (p.Arg737Ter)
Variation ID: 2361 Accession: VCV000002361.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q41 1: 216247185 (GRCh38) [ NCBI UCSC ] 1: 216420527 (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 Nov 12, 2015 Apr 6, 2024 Mar 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_206933.4:c.2209C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_996816.3:p.Arg737Ter nonsense NM_007123.6:c.2209C>T NP_009054.6:p.Arg737Ter nonsense NC_000001.11:g.216247185G>A NC_000001.10:g.216420527G>A NG_009497.2:g.181264C>T - Protein change
- R737*
- Other names
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- Canonical SPDI
- NC_000001.11:216247184:G: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
6937 | 8412 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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Mar 29, 2024 | RCV000002456.14 | |
Pathogenic (3) |
criteria provided, single submitter
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Sep 11, 2023 | RCV000002457.8 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Sep 8, 2023 | RCV000725261.11 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 23, 2019 | RCV001003279.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 10, 2009 | RCV000824794.4 |
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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Pathogenic
(Nov 10, 2009)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000065505.6
First in ClinVar: May 03, 2013 Last updated: Aug 26, 2019 |
Number of individuals with the variant: 1
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Pathogenic
(Feb 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 2A
Affected status: yes
Allele origin:
germline
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Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals
Accession: SCV001156378.1
First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Congenital sensorineural hearing impairment (present) , Progressive night blindness (present) , Peripheral visual field loss (present) , Rod-cone dystrophy (present)
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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: SCV004182449.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Sep 08, 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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Invitae
Accession: SCV001218779.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2361). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2361). This premature translational stop signal has been observed in individual(s) with Usher syndrome and autosomal recessive retinitis pigmentosa (PMID: 17296898, 25356976, 29490346). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs111033334, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg737*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). (less)
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Pathogenic
(Oct 01, 2015)
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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: SCV000335428.4
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
(Aug 28, 2023)
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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: SCV004030739.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023 |
Comment:
Observed in many patients with Usher syndrome in published literature (Kaiserman N et al., 2007; Lenassi E et al., 2015; Bonnet C et al., 2016; … (more)
Observed in many patients with Usher syndrome in published literature (Kaiserman N et al., 2007; Lenassi E et al., 2015; Bonnet C et al., 2016; Khalaileh A et al., 2018); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 32036094, 32675063, 18452394, 30685615, 24516651, 25356976, 24944099, 17296898, 31456290, 27460420, 25649381, 29490346, 33576794, 34781295, 31964843, 36460718, 36819107) (less)
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Pathogenic
(Sep 11, 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: SCV004208272.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Mar 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 2A
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004807566.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Feb 01, 2007)
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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: SCV000022614.3
First in ClinVar: Apr 04, 2013 Last updated: Nov 12, 2015 |
Comment on evidence:
For discussion of the arg737-to-ter (R737X) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members … (more)
For discussion of the arg737-to-ter (R737X) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members had Usher syndrome type IIa (USH2A; 276901) and others had nonsyndromic retinitis pigmentosa (RP39; 613809) by Kaiserman et al. (2007), see 608400.0010. (less)
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Pathogenic
(Feb 01, 2007)
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no assertion criteria provided
Method: literature only
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RETINITIS PIGMENTOSA 39
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022615.3
First in ClinVar: Apr 04, 2013 Last updated: Nov 12, 2015 |
Comment on evidence:
For discussion of the arg737-to-ter (R737X) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members … (more)
For discussion of the arg737-to-ter (R737X) mutation in the USH2A gene that was found in compound heterozygous state in a family in which some members had Usher syndrome type IIa (USH2A; 276901) and others had nonsyndromic retinitis pigmentosa (RP39; 613809) by Kaiserman et al. (2007), see 608400.0010. (less)
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Pathogenic
(Jan 16, 2018)
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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: SCV000797194.2
First in ClinVar: Aug 05, 2018 Last updated: Dec 23, 2019 |
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Pathogenic
(Jun 23, 2019)
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no assertion criteria provided
Method: research
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Usher syndrome type 2
Affected status: yes
Allele origin:
inherited
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Sharon lab, Hadassah-Hebrew University Medical Center
Accession: SCV001161362.1
First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020 |
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Pathogenic
(Nov 05, 2020)
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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: SCV002093960.1
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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The Genetics of Usher Syndrome in the Israeli and Palestinian Populations. | Khalaileh A | Investigative ophthalmology & visual science | 2018 | PMID: 29490346 |
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 |
A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants. | Lenassi E | European journal of human genetics : EJHG | 2015 | PMID: 25649381 |
Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing. | Huang XF | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25356976 |
Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots. | Baux D | Human mutation | 2014 | PMID: 24944099 |
Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. | McGee TL | Journal of medical genetics | 2010 | PMID: 20507924 |
Four USH2A founder mutations underlie the majority of Usher syndrome type 2 cases among non-Ashkenazi Jews. | Auslender N | Genetic testing | 2008 | PMID: 18452394 |
Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2. | Kaiserman N | Archives of ophthalmology (Chicago, Ill. : 1960) | 2007 | PMID: 17296898 |
Identification of novel USH2A mutations: implications for the structure of USH2A protein. | Dreyer B | European journal of human genetics : EJHG | 2000 | PMID: 10909849 |
Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa. | Weston MD | American journal of human genetics | 2000 | PMID: 10729113 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=USH2A | - | - | - | - |
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Text-mined citations for rs111033334 ...
HelpRecord last updated Apr 06, 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.