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

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 3, 2017
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:
RCV000824781.6

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]
Observations:
8

Condition(s)

Name:
Usher syndrome
Synonyms:
Usher Syndromes; Usher's syndrome
Identifiers:
MONDO: MONDO:0019501; MeSH: D052245; MedGen: C0271097; Orphanet: 886; OMIM: PS276900
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
SCV000065401Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Oct 3, 2017) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided88not providednot providednot providedclinical testing

Citations

PubMed

Development of a genotyping microarray for Usher syndrome.

Cremers FP, Kimberling WJ, Külm M, de Brouwer AP, van Wijk E, te Brinke H, Cremers CW, Hoefsloot LH, Banfi S, Simonelli F, Fleischhauer JC, Berger W, Kelley PM, Haralambous E, Bitner-Glindzicz M, Webster AR, Saihan Z, De Baere E, Leroy BP, Silvestri G, McKay GJ, Koenekoop RK, et al.

J Med Genet. 2007 Feb;44(2):153-60. Epub 2006 Sep 8.

PubMed [citation]
PMID:
16963483
PMCID:
PMC2598068

Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.

van Wijk E, Pennings RJ, te Brinke H, Claassen A, Yntema HG, Hoefsloot LH, Cremers FP, Cremers CW, Kremer H.

Am J Hum Genet. 2004 Apr;74(4):738-44. Epub 2004 Mar 10.

PubMed [citation]
PMID:
15015129
PMCID:
PMC1181950
See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000065401.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided8not providednot providedclinical testing PubMed (6)

Description

The p.Trp3955X variant in USH2A has been reported in many probands with Usher sy ndrome, many of whom were homozygous or compound heterozygous (van Wijk 2004, Cr emers 2007, Jacobson 2008, Dreyer 2008, Jaijo 2009, LMM data). This variant has also been identified in 0.025% (32/128914) of European chromosomes, including 1 homozygote, by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is not high enough to ru le out a pathogenic role. This nonsense variant leads to a premature termination codon at position 3955, which is predicted to lead to a truncated or absent pro tein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome. ACMG/AMP Criteria applied: PVS1, PM3_Very S trong, PP4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided8not provided8not provided

Last Updated: Oct 26, 2024