Published functional studies suggest a damaging effect on gene splicing (Le Guedard-Mereuze et al., 2010); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 31589614, 28944237, 20052763, 27957503, 25078356, 22334370, 24944099, 31964843)
ClinVar Genomic variation as it relates to human health
NM_206933.4(USH2A):c.486-14G>A
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic/Likely pathogenic
9 out of 12 submissions contributed to this classification
Help
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.
12
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_206933.4(USH2A):c.486-14G>A
Variation ID: 372543 Accession: VCV000372543.46
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1q41 1: 216418693 (GRCh38) [ NCBI UCSC ] 1: 216592035 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jan 9, 2017 Oct 25, 2025 Jul 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_206933.4:c.486-14G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_007123.6:c.486-14G>A intron variant NC_000001.11:g.216418693C>T NC_000001.10:g.216592035C>T NG_009497.2:g.9756G>A - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000001.11:216418692:C:T
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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.
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The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00005
Trans-Omics for Precision Medicine (TOPMed) 0.00005
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- 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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| USH2A | Gene associated with autosomal recessive phenotype | Not yet evaluated |
GRCh38 GRCh37 |
7821 | 9478 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2024 | RCV000414183.37 | |
| Likely pathogenic (1) |
no assertion criteria provided
|
Mar 23, 2018 | RCV000673542.3 | |
| Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 7, 2019 | RCV001075754.4 | |
| Likely pathogenic (2) |
criteria provided, single submitter
|
Apr 11, 2023 | RCV001828379.3 | |
| Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Aug 5, 2023 | RCV000678652.6 |
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. |
Expand all rows
Collapse all rows
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jun 07, 2019)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Retinal dystrophy |
Blueprint Genetics
Accession: SCV001241384.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Oct 06, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Retinitis pigmentosa 39 |
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001934220.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: yes
|
|
|
Likely pathogenic
(Apr 11, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Retinitis pigmentosa 39 |
Genome-Nilou Lab
Accession: SCV004172222.1
First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
|
|
|
Likely pathogenic
(Apr 11, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Usher syndrome type 2A |
Genome-Nilou Lab
Accession: SCV004172224.1
First in ClinVar: Dec 09, 2023 Last updated: Dec 09, 2023 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: no
|
|
|
Pathogenic
(Aug 05, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Retinitis pigmentosa 39 |
Baylor Genetics
Accession: SCV004208351.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Likely pathogenic
(Jan 01, 2014)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Retinal dystrophy |
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Accession: SCV005070472.1
First in ClinVar: Dec 28, 2024 Last updated: Dec 28, 2024 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Likely pathogenic
(Sep 28, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Not Provided |
GeneDx
Accession: SCV000490866.3
First in ClinVar: Jan 09, 2017 Last updated: Sep 16, 2024 |
Comment:
show
Published functional studies suggest a damaging effect on gene splicing (Le Guedard-Mereuze et al., 2010); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 31589614, 28944237, 20052763, 27957503, 25078356, 22334370, 24944099, 31964843) (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Jul 01, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001236140.6
First in ClinVar: Apr 15, 2020 Last updated: Feb 25, 2025 |
Comment:
show
This sequence change falls in intron 2 of the USH2A gene. It does not directly change the encoded amino acid sequence of the USH2A protein. This variant is present in population databases (rs374536346, gnomAD 0.009%). This variant has been observed in individual(s) with retinitis pigmentosa and/or Usher syndrome (PMID: 22334370, 27957503). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372543). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20052763). For these reasons, this variant has been classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Sep 01, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001961166.28
First in ClinVar: Oct 08, 2021 Last updated: Oct 25, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Sep 01, 2016)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Retinitis pigmentosa 39 |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Accession: SCV000804743.2
First in ClinVar: Sep 10, 2018 Last updated: Sep 10, 2018 |
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: yes
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Dec 28, 2020)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Usher syndrome type 2A |
Natera, Inc.
Accession: SCV002094029.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Likely pathogenic
(Mar 23, 2018)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Usher syndrome type 2A
Retinitis pigmentosa 39 |
Counsyl
Accession: SCV000798754.2
First in ClinVar: Aug 05, 2018 Last updated: Jun 29, 2025 |
Comment:
show
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
Comment:
Comment:
This sequence change falls in intron 2 of the USH2A gene. It does not directly change the encoded amino acid sequence of the USH2A protein. This variant is present in population databases (rs374536346, gnomAD 0.009%). This variant has been observed in individual(s) with retinitis pigmentosa and/or Usher syndrome (PMID: 22334370, 27957503). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372543). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20052763). For these reasons, this variant has been classified as Pathogenic.
Comment:
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases. | Hanany M | Proceedings of the National Academy of Sciences of the United States of America | 2020 | PMID: 31964843 |
| Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. | Capalbo A | PLoS genetics | 2019 | PMID: 31589614 |
| 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 |
| Usher syndrome in Denmark: mutation spectrum and some clinical observations. | Dad S | Molecular genetics & genomic medicine | 2016 | PMID: 27957503 |
| 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 |
| Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots. | Baux D | Human mutation | 2014 | PMID: 24944099 |
| A genetic basis for mechanosensory traits in humans. | Frenzel H | PLoS biology | 2012 | PMID: 22563300 |
| Next-generation genetic testing for retinitis pigmentosa. | Neveling K | Human mutation | 2012 | PMID: 22334370 |
| Ex vivo splicing assays of mutations at noncanonical positions of splice sites in USHER genes. | Le Guédard-Méreuze S | Human mutation | 2010 | PMID: 20052763 |
Text-mined citations for rs374536346 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 26, 2025
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.