ClinVar Genomic variation as it relates to human health
NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)
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
-
NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)
Variation ID: 2357 Accession: VCV000002357.72
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q41 1: 215728232 (GRCh38) [ NCBI UCSC ] 1: 215901574 (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 Jun 17, 2024 Mar 20, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_206933.4:c.11864G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_996816.3:p.Trp3955Ter nonsense NC_000001.11:g.215728232C>T NC_000001.10:g.215901574C>T NG_009497.2:g.700217G>A - Protein change
- W3955*
- Other names
- -
- Canonical SPDI
- NC_000001.11:215728231:C: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.
The Genome Aggregation Database (gnomAD), exomes 0.00009
Exome Aggregation Consortium (ExAC) 0.00011
Trans-Omics for Precision Medicine (TOPMed) 0.00011
The Genome Aggregation Database (gnomAD) 0.00012
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
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. |
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USH2A | - | - |
GRCh38 GRCh37 |
7022 | 8508 |
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 (11) |
criteria provided, multiple submitters, no conflicts
|
Nov 4, 2023 | RCV000002451.26 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jul 23, 2014 | RCV000414867.4 | |
Pathogenic (1) |
no assertion criteria provided
|
Feb 12, 2016 | RCV000415089.4 | |
Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000414231.39 | |
Pathogenic (3) |
criteria provided, single submitter
|
Apr 1, 2021 | RCV000504922.6 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 20, 2024 | RCV000412373.7 | |
Pathogenic (1) |
criteria provided, single submitter
|
Aug 7, 2019 | RCV001074873.4 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 3, 2017 | RCV000824781.6 | |
Pathogenic (1) |
no assertion criteria provided
|
Jun 23, 2019 | RCV001003260.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 11, 2021 | RCV001806999.3 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 9, 2023 | RCV001813732.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 11, 2023 | RCV003114173.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 23, 2022 | RCV002476913.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 13, 2023 | RCV003314546.3 | |
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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
(Aug 30, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000344373.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 5
Sex: mixed
|
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Pathogenic
(Oct 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Rare genetic deafness
Usher syndrome (Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000065401.6
First in ClinVar: May 03, 2013 Last updated: Aug 26, 2019 |
Comment:
The p.Trp3955X variant in USH2A has been reported in many probands with Usher sy ndrome, many of whom were homozygous or compound heterozygous (van Wijk … (more)
The p.Trp3955X variant in USH2A has been reported in many probands with Usher sy ndrome, many of whom were homozygous or compound heterozygous (van Wijk 2004, Cr emers 2007, Jacobson 2008, Dreyer 2008, Jaijo 2009, LMM data). This variant has also been identified in 0.025% (32/128914) of European chromosomes, including 1 homozygote, by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is not high enough to ru le out a pathogenic role. This nonsense variant leads to a premature termination codon at position 3955, which is predicted to lead to a truncated or absent pro tein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome. ACMG/AMP Criteria applied: PVS1, PM3_Very S trong, PP4. (less)
Number of individuals with the variant: 8
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Pathogenic
(Apr 08, 2021)
|
criteria provided, single submitter
Method: research
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Retinitis pigmentosa 39
Affected status: yes
Allele origin:
germline
|
Ocular Genomics Institute, Massachusetts Eye and Ear
Accession: SCV001573517.1
First in ClinVar: May 10, 2021 Last updated: May 10, 2021 |
Comment:
The USH2A c.11864G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we … (more)
The USH2A c.11864G>A 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, PP3, PP4. Based on this evidence we have classified this variant as Pathogenic. (less)
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Pathogenic
(Apr 01, 2021)
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criteria provided, single submitter
Method: curation
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Retinitis pigmentosa
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001950398.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The p.Trp3955Ter variant in USH2A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics … (more)
The p.Trp3955Ter variant in USH2A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3, PP3, PP4. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. (less)
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Pathogenic
(Jan 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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USH2A-related disorder
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002061201.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
The c.11864G>A;p.(Trp3955*) variant creates a premature translational stop signal in the USH2A gene. It is expected to result in an absent or disrupted protein product … (more)
The c.11864G>A;p.(Trp3955*) variant creates a premature translational stop signal in the USH2A gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID:2357; PMID: 29293505; 27460420; 26927203; 25649381; 25575603; 25333064; 22135276; 21569298; 20507924) - PS4. The variant is present at low allele frequencies population databases (rs111033364 – gnomAD 0.01249%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Trp3955*) was detected in trans with a pathogenic variant (PMID: 29293505; 27460420; 25649381; 25575603; 25333064; 22135276; 21569298) - PM3_strong. The variant co-segregated with disease in multiple affected family members (PMID: 25575603) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Pathogenic
(Jan 13, 2022)
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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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Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV002577544.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Comment:
PVS1, PM2, PP3, PP5
|
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Pathogenic
(Mar 11, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556531.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
|
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Pathogenic
(Jan 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003801311.2
First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023 |
Comment:
Variant summary: USH2A c.11864G>A (p.Trp3955X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: USH2A c.11864G>A (p.Trp3955X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 9.2e-05 in 251168 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in USH2A causing Usher Syndrome (9.2e-05 vs 0.011), allowing no conclusion about variant significance. c.11864G>A has been reported in the literature as biallelic homozygous or compound heterozygous genotypes in multiple individuals affected with Usher Syndrome (example, PMID: 27460420, 28944237). These data indicate that the variant is very likely to be associated with disease. Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jan 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 3A
Affected status: unknown
Allele origin:
unknown
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Illumina Laboratory Services, Illumina
Accession: SCV004014696.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
The USH2A c.11864G>A (p.Trp3955Ter) nonsense variant results in the loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The c.11864G>A variant … (more)
The USH2A c.11864G>A (p.Trp3955Ter) nonsense variant results in the loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. The c.11864G>A variant is a founder variant in central European and is particularly common in the Slovenian population, where it has been estimated to account for over 80% disease-causing alleles among individuals with Usher syndrome type 2 (PMID: 27460420; PMID: 31817543). Across a selection of the available literature, the c.11864G>A variant is most commonly reported in association with Usher syndrome type 2, but has also been reported in individuals with non-syndromic retinitis pigmentosa (PMID: 15015129; PMID: 2564938; PMID: 27460420; PMID: 31817543). The highest frequency of this allele in the Genome Aggregation Database is 0.000279 in the European (non-Finnish) population, which includes one homozygote (version 3.1.2). Based on the available evidence, the c.11864G>A (p.Trp3955Ter) variant is classified as pathogenic for Usher syndrome type 2. (less)
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Pathogenic
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246247.22
First in ClinVar: May 09, 2020 Last updated: Jun 17, 2024 |
Comment:
USH2A: PM3:Very Strong, PVS1, PM2
Number of individuals with the variant: 19
|
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Pathogenic
(Jul 23, 2014)
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criteria provided, single submitter
Method: clinical testing
|
Hearing impairment
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000492761.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: unknown
Allele origin:
germline
|
Baylor Genetics
Accession: SCV001162877.1
First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020 |
|
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Pathogenic
(Aug 07, 2019)
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criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001240477.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
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Pathogenic
(Dec 26, 2019)
|
criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 2A
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV001194132.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 04, 2020 |
Comment:
NM_206933.2(USH2A):c.11864G>A(W3955*) is classified as pathogenic in the context of USH2A-related disorders. Sources cited for classification include the following: PMID 27460420. Classification of NM_206933.2(USH2A):c.11864G>A(W3955*) is based … (more)
NM_206933.2(USH2A):c.11864G>A(W3955*) is classified as pathogenic in the context of USH2A-related disorders. Sources cited for classification include the following: PMID 27460420. Classification of NM_206933.2(USH2A):c.11864G>A(W3955*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446857.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Rod-cone dystrophy (present)
Sex: female
|
|
Pathogenic
(Oct 21, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366417.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2.
|
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Pathogenic
(May 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Rod-cone dystrophy
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, University Hospital Muenster
Accession: SCV002054109.1
First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022 |
Comment:
ACMG categories: PVS1,PM2,PM3,PP3,PP5
Number of individuals with the variant: 1
Age: 20-29 years
Sex: male
Tissue: blood
|
|
Pathogenic
(Sep 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002581855.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4, PM3_STR, PM2_SUP, PP1
|
Number of individuals with the variant: 2
Sex: male
|
|
Pathogenic
(Nov 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: yes
Allele origin:
germline
|
The Shared Resource Centre "Genome", Research Centre for Medical Genetics
Accession: SCV002756439.1
First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022 |
Number of individuals with the variant: 6
|
|
Pathogenic
(Mar 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Retinitis pigmentosa 39
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002787205.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
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Pathogenic
(Feb 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000490872.5
First in ClinVar: Jan 09, 2017 Last updated: Mar 04, 2023 |
Comment:
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; This … (more)
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; This variant is associated with the following publications: (PMID: 25262649, 19683999, 28944237, 29293505, 31817543, 25575603, 22135276, 18273898, 18463160, 26927203, 28749477, 29551606, 28945494, 29986705, 28984810, 28559085, 31370859, 15015129, 16963483, 31054281, 31266775, 31456290, 32581362, 32188678, 34426522, 33089500, 31589614, 33576794, 33105617, 33737949, 32037395) (less)
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Pathogenic
(Nov 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 39
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV004182063.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
|
|
Pathogenic
(Nov 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 2A
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV004182064.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
|
|
Pathogenic
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001213203.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp3955*) in the USH2A gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Trp3955*) 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). This variant is present in population databases (rs111033364, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individuals with Usher syndrome (PMID: 22135276, 25575603, 29293505). ClinVar contains an entry for this variant (Variation ID: 2357). For these reasons, this variant has been classified as Pathogenic. (less)
|
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Pathogenic
(Nov 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
USH2A-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004718566.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The USH2A c.11864G>A variant is predicted to result in premature protein termination (p.Trp3955*). This variant has been reported many times in individuals with Usher syndrome … (more)
The USH2A c.11864G>A variant is predicted to result in premature protein termination (p.Trp3955*). This variant has been reported many times in individuals with Usher syndrome and is noted to be one of the most common pathogenic variants in USH2A, being detected in ~22% of a cohort of patients (see for examples Bonnet et al. 2016. PubMed ID: 27460420; Lenarduzzi et al. 2015. PubMed ID: 25575603; Table S4 in Stone et al. 2017. PubMed ID: 28559085). This variant is reported in 0.025% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-215901574-C-T). Nonsense variants in USH2A are expected to be pathogenic. Given the evidence, we interpret this variant as pathogenic. (less)
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Pathogenic
(Mar 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 39
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004207697.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
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Pathogenic
(Apr 01, 2004)
|
no assertion criteria provided
Method: literature only
|
USHER SYNDROME, TYPE IIA
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022609.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 14, 2018 |
Comment on evidence:
In 2 patients with Usher syndrome type IIa (USH2A; 276901), van Wijk et al. (2004) found compound heterozygosity for a trp3955-to-ter (W3955X) mutation in the … (more)
In 2 patients with Usher syndrome type IIa (USH2A; 276901), van Wijk et al. (2004) found compound heterozygosity for a trp3955-to-ter (W3955X) mutation in the USH2A gene and 2 different mutations: a 949C-A transversion in one patient, resulting in an arg317-to-arg mutation (R317R; 608400.0008), which was predicted to create an additional 5-prime splice site in exon 5; and a 1256G-T transversion, resulting in a cys419-to-phe substitution (C419F; 608400.0009) in the second patient. (less)
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Pathogenic
(Apr 01, 2018)
|
no assertion criteria provided
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
|
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926715.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
|
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Pathogenic
(Jun 23, 2019)
|
no assertion criteria provided
Method: research
|
Usher syndrome type 2
Affected status: yes
Allele origin:
inherited
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Sharon lab, Hadassah-Hebrew University Medical Center
Accession: SCV001161342.1
First in ClinVar: Feb 16, 2020 Last updated: Feb 16, 2020 |
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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 DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974079.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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Pathogenic
(Feb 12, 2016)
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no assertion criteria provided
Method: clinical testing
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Congenital sensorineural hearing impairment
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000492673.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
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Pathogenic
(Jan 01, 2015)
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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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NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598770.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: European
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Pathogenic
(Oct 27, 2016)
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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: SCV000487752.2
First in ClinVar: Jan 06, 2017 Last updated: Jan 06, 2017 |
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Pathogenic
(Sep 16, 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: SCV001451982.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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: SCV001956064.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Oct 30, 2023)
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no assertion criteria provided
Method: clinical testing
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Usher syndrome type 2A
Affected status: yes
Allele origin:
germline
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Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004099463.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
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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 importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK). | Zampaglione E | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 34906470 |
Clinical and Haplotypic Variability of Slovenian USH2A Patients Homozygous for the c. 11864G>A Nonsense Mutation. | Zupan A | Genes | 2019 | PMID: 31817543 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss. | Likar T | PloS one | 2018 | PMID: 29293505 |
Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome. | Neuhaus C | Molecular genetics & genomic medicine | 2017 | PMID: 28944237 |
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 |
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 |
Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis. | Lenarduzzi S | Hearing research | 2015 | PMID: 25575603 |
Screening for single nucleotide variants, small indels and exon deletions with a next-generation sequencing based gene panel approach for Usher syndrome. | Krawitz PM | Molecular genetics & genomic medicine | 2014 | PMID: 25333064 |
Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. | Shearer AE | American journal of human genetics | 2014 | PMID: 25262649 |
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study. | Le Quesne Stabej P | Journal of medical genetics | 2012 | PMID: 22135276 |
Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. | Bonnet C | Orphanet journal of rare diseases | 2011 | PMID: 21569298 |
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 |
Microarray-based mutation analysis of 183 Spanish families with Usher syndrome. | Jaijo T | Investigative ophthalmology & visual science | 2010 | PMID: 19683999 |
Mutation analysis in the long isoform of USH2A in American patients with Usher Syndrome type II. | Yan D | Journal of human genetics | 2009 | PMID: 19881469 |
Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene. | Sandberg MA | Investigative ophthalmology & visual science | 2008 | PMID: 18641288 |
Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism. | Jacobson SG | Human molecular genetics | 2008 | PMID: 18463160 |
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 |
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 |
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 |
Third World debts. | Chan M | Lancet (London, England) | 1989 | PMID: 2564938 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=USH2A | - | - | - | - |
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Text-mined citations for rs111033364 ...
HelpRecord last updated Jun 30, 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.