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NM_206933.4(USH2A):c.11241C>A (p.Tyr3747Ter) AND Rare genetic deafness

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 30, 2018
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:
RCV000605356.4

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_009497.2:g.669706C>A
  • NM_206933.4:c.11241C>AMANE SELECT
  • NP_996816.2:p.Tyr3747Ter
  • NP_996816.3:p.Tyr3747Ter
  • NC_000001.10:g.215932085G>T
  • NG_009497.1:g.669654C>A
  • NM_206933.2:c.11241C>A
  • NM_206933.3:c.11241C>A
  • p.Tyr3747X
Protein change:
Y3747*
Links:
dbSNP: rs777465132
NCBI 1000 Genomes Browser:
rs777465132
Molecular consequence:
  • NM_206933.4:c.11241C>A - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: C5680250; Orphanet: 96210

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000713838Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Jan 30, 2018) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000713838.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.Tyr3747X variant in USH2A has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 0.02% (4/24020) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad .broadinstitute.org; dbSNP rs777465132). This nonsense variant leads to a premat ure termination codon at position 3747, which is predicted to lead to a truncate d or absent protein. Variants in USH2A resulting in a loss of function of the pr otein is an established disease mechanism in autosomal recessive Usher syndrome. In addition, this variant is likely in trans with the deletion of exons 63-64 i n USH2A given that previous cases with the deletion did not carry this variant. This provides additional evidence that the variant is pathogenic. In summary, th is variant meets our criteria to be classified as pathogenic for autosomal reces sive Usher syndrome. ACMG/AMP Criteria applied: PVS1; PM2; PM3.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Feb 20, 2024