ClinVar Genomic variation as it relates to human health
NM_206933.4(USH2A):c.15428G>A (p.Arg5143His)
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.15428G>A (p.Arg5143His)
Variation ID: 48463 Accession: VCV000048463.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q41 1: 215628905 (GRCh38) [ NCBI UCSC ] 1: 215802247 (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 May 29, 2016 Feb 20, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_206933.4:c.15428G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_996816.3:p.Arg5143His missense NC_000001.11:g.215628905C>T NC_000001.10:g.215802247C>T NG_009497.2:g.799544G>A O75445:p.Arg5143His - Protein change
- R5143H
- Other names
- p.R5143H:CGC>CAC
- Canonical SPDI
- NC_000001.11:215628904: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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0.01757 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00492
Trans-Omics for Precision Medicine (TOPMed) 0.01574
1000 Genomes Project 0.01757
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01799
1000 Genomes Project 30x 0.01858
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 |
6944 | 8419 |
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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Benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 22, 2022 | RCV000041786.20 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000883059.25 | |
Benign (2) |
criteria provided, single submitter
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Nov 4, 2023 | RCV001276137.10 | |
Benign (1) |
criteria provided, single submitter
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Nov 4, 2023 | RCV003450821.1 |
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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Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001026334.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024 |
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Benign
(Jul 17, 2019)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV001146605.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
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Benign
(Nov 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000605552.4
First in ClinVar: May 29, 2016 Last updated: Feb 20, 2024 |
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Benign
(Mar 20, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000860033.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(Jan 11, 2012)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000065482.6
First in ClinVar: May 03, 2013 Last updated: May 29, 2016 |
Comment:
Arg5143His in exon 71 of USH2A: This variant has been reported in 2/80 individua ls with non-syndromic retinitis pigmentosa (McGee 2010); however, this variant i … (more)
Arg5143His in exon 71 of USH2A: This variant has been reported in 2/80 individua ls with non-syndromic retinitis pigmentosa (McGee 2010); however, this variant i s not expected to have clinical significance because it has been identified in 5 .1% (188/3738) of African American control chromosomes by the NHBLI Exome sequen cing project (http://evs.gs.washington.edu/EVS; dbSNP rs111033435). (less)
Number of individuals with the variant: 15
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Benign
(Jan 16, 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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GeneDx
Accession: SCV000169777.10
First in ClinVar: Jun 23, 2014 Last updated: May 29, 2016 |
Comment:
This variant is associated with the following publications: (PMID: 27460420, 29024829)
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Benign
(Feb 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002104141.1
First in ClinVar: Mar 12, 2022 Last updated: Mar 12, 2022 |
Comment:
Variant summary: USH2A c.15428G>A (p.Arg5143His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging … (more)
Variant summary: USH2A c.15428G>A (p.Arg5143His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0039 in 251468 control chromosomes (gnomAD), predominantly at a frequency of 0.054 within the African or African-American subpopulation in the gnomAD database, including 31 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.87 fold of the estimated maximal expected allele frequency for a pathogenic variant in USH2A causing the Usher Syndrome phenotype (0.011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Six ClinVar submitters have assessed the variant since 2014: all have classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. (less)
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Benign
(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: SCV004182697.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Benign
(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: SCV004182708.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
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Benign
(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: SCV001461989.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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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 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=USH2A | - | - | - | - |
Text-mined citations for rs111033435 ...
HelpRecord last updated May 27, 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.