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NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter) AND Usher syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 11, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003114173.5

Allele description [Variation Report for NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)]

NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)

Gene:
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)
HGVS:
  • NC_000001.11:g.215728232C>T
  • NG_009497.2:g.700217G>A
  • NM_206933.4:c.11864G>AMANE SELECT
  • NP_996816.3:p.Trp3955Ter
  • NC_000001.10:g.215901574C>T
  • NG_009497.1:g.700165G>A
  • NM_206933.2:c.11864G>A
  • NM_206933.3:c.11864G>A
  • c.11864G>A
  • p.Trp3955X
Protein change:
W3955*; TRP3955TER
Links:
OMIM: 608400.0007; dbSNP: rs111033364
NCBI 1000 Genomes Browser:
rs111033364
Molecular consequence:
  • NM_206933.4:c.11864G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Usher syndrome
Synonyms:
Usher Syndromes; Usher's syndrome
Identifiers:
MONDO: MONDO:0019501; MeSH: D052245; MedGen: C0271097; Orphanet: 886; OMIM: PS276900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003801311Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Jan 11, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C, Lefèvre GM, Hardelin JP, El-Amraoui A, Singh-Estivalet A, Mohand-Saïd S, Kohl S, Kurtenbach A, Sliesoraityte I, Zobor D, Gherbi S, Testa F, Simonelli F, Banfi S, Fakin A, Glavač D, Jarc-Vidmar M, et al.

Eur J Hum Genet. 2016 Dec;24(12):1730-1738. doi: 10.1038/ejhg.2016.99. Epub 2016 Jul 27.

PubMed [citation]
PMID:
27460420
PMCID:
PMC5117943

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, Eisenberger T, Decker C, Nagl S, Blank C, Pfister M, Kennerknecht I, Müller-Hofstede C, Charbel Issa P, Heller R, Beck B, Rüther K, Mitter D, Rohrschneider K, Steinhauer U, Korbmacher HM, Huhle D, Elsayed SM, Taha HM, Baig SM, Stöhr H, Preising M, et al.

Mol Genet Genomic Med. 2017 Sep;5(5):531-552. doi: 10.1002/mgg3.312.

PubMed [citation]
PMID:
28944237
PMCID:
PMC5606877

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003801311.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 26, 2024