ClinVar Genomic variation as it relates to human health
NM_206933.4(USH2A):c.5399G>A (p.Trp1800Ter)
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.5399G>A (p.Trp1800Ter)
Variation ID: 556449 Accession: VCV000556449.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q41 1: 216078262 (GRCh38) [ NCBI UCSC ] 1: 216251604 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 5, 2018 Apr 15, 2024 Nov 4, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_206933.4:c.5399G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_996816.3:p.Trp1800Ter nonsense NC_000001.11:g.216078262C>T NC_000001.10:g.216251604C>T NG_009497.2:g.350187G>A - Protein change
- W1800*
- Other names
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- Canonical SPDI
- NC_000001.11:216078261: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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
- Links
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 |
6918 | 8387 | |
USH2A-AS2 | - | - | - | GRCh38 | - | 548 |
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
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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 (1) |
criteria provided, single submitter
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Jan 31, 2018 | RCV000672460.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 3, 2019 | RCV001074797.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jul 29, 2023 | RCV001091135.18 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 4, 2023 | RCV002272322.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 8, 2022 | RCV002469251.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 4, 2023 | RCV003453347.2 |
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
(Jan 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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Counsyl
Accession: SCV000797566.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(Jul 03, 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: SCV001240394.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(Apr 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 2A
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556744.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
Comment:
The USH2A c.5399G>A variant is classified as PATHOGENIC (PVS1, PS4, PM3) The USH2A c.5399G>A variant is a single nucleotide change which is predicted to result … (more)
The USH2A c.5399G>A variant is classified as PATHOGENIC (PVS1, PS4, PM3) The USH2A c.5399G>A variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 1800 (PVS1). The variant has been reported in several individuals with a clinical presentation of Usher syndrome, type 2A (PMID:24944099; 32531858) (PS4). This variant has been detected in trans with another pathogenic variant for this recessive condition in both this individual and in other reported cases in the literature (PM3). This variant is in dbSNP (rs1553299079) and has been reported in population databases (gnomAD 2/152142 allelels, no homozygotes. This variant has been reported in ClinVar as pathogenic for Usher syndrome and retinal dystrophy by other diagnostic laboratories (ClinVar Variation ID: 556449) and as damaging for Usher syndrome 2 in the disease database HGMD (CM149920). (less)
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Pathogenic
(Nov 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002766561.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Variant summary: USH2A c.5399G>A (p.Trp1800X) 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.5399G>A (p.Trp1800X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250992 control chromosomes (gnomAD). c.5399G>A has been reported in the literature in individuals affected with Usher Syndrome and Retinitis Pigmentosa (Baux_2014, Lenarduzzi_2015, Weisschuh_2020, Mansard_2021). Multiple patients were reported as compound heterozygous, carrying a second (likely) pathogenic variant, and at least one of which was confirmed in trans based on parental testing. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (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: SCV004181813.1
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: SCV004181815.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Mar 15, 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: SCV004206289.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jul 29, 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: SCV003524080.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Trp1800*) 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.Trp1800*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 24944099, 25575603). ClinVar contains an entry for this variant (Variation ID: 556449). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 01, 2017)
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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: SCV001247004.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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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 Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A. | Mansard L | International journal of molecular sciences | 2021 | PMID: 34948090 |
Genetic architecture of inherited retinal degeneration in Germany: A large cohort study from a single diagnostic center over a 9-year period. | Weisschuh N | Human mutation | 2020 | PMID: 32531858 |
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 |
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 |
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 |
Text-mined citations for rs1553299079 ...
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.