NM_206933.4(USH2A):c.11241C>A (p.Tyr3747Ter) AND Usher syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 17, 2018)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000710334.1

Allele description [Variation Report for NM_206933.4(USH2A):c.11241C>A (p.Tyr3747Ter)]

NM_206933.4(USH2A):c.11241C>A (p.Tyr3747Ter)

Gene:
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.11241C>A (p.Tyr3747Ter)
Other names:
NM_206933.2(USH2A):c.11241C>A(p.Tyr3747Ter); NM_206933.2(USH2A):c.11241C>A
HGVS:
  • NC_000001.11:g.215758743G>T
  • NG_009497.1:g.669654C>A
  • NG_009497.2:g.669706C>A
  • NM_206933.3:c.11241C>A
  • NM_206933.4:c.11241C>AMANE SELECT
  • NP_996816.2:p.Tyr3747Ter
  • NP_996816.3:p.Tyr3747Ter
  • NC_000001.10:g.215932085G>T
  • NM_206933.2:c.11241C>A
  • p.Tyr3747X
Protein change:
Y3747*
Links:
dbSNP: rs777465132
NCBI 1000 Genomes Browser:
rs777465132
Molecular consequence:
  • NM_206933.3:c.11241C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_206933.4:c.11241C>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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000840528ClinGen Hearing Loss Variant Curation Expert Panelreviewed by expert panel
Pathogenic
(Sep 17, 2018)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Hearing Loss Variant Curation Expert Panel, SCV000840528.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The p.Tyr3747X variant in USH2A is predicted to cause a premature stop codon in biologically-relevant-exon 58/72 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). The allele frequency of the p.Tyr3747X variant in the Ush2A gene is 0.017% (4/24020) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org), which is a low enough frequency to award PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss ( PM2_Supporting). This variant has been detected in 1 patient with hearing loss in trans with a suspected pathogenic variant (PM3_Supporting, Partners LMM internal data SCV000713838.1). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied: PVS1, PM2_Supporting, PM3_Supporting.

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

Last Updated: Oct 30, 2021

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