NM_206933.4(USH2A):c.2332G>T (p.Asp778Tyr) AND Usher syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 14, 2021
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:: RCV001804867.9

Allele description [Variation Report for NM_206933.4(USH2A):c.2332G>T (p.Asp778Tyr)]

NM_206933.4(USH2A):c.2332G>T (p.Asp778Tyr)

Genes:

LOC122152296:Sharpr-MPRA regulatory region 8762 [Gene]
USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.2332G>T (p.Asp778Tyr)

HGVS:

NC_000001.11:g.216247062C>A
NG_009497.2:g.181387G>T
NM_007123.6:c.2332G>T
NM_206933.4:c.2332G>TMANE SELECT
NP_009054.6:p.Asp778Tyr
NP_996816.3:p.Asp778Tyr
NC_000001.10:g.216420404C>A
NG_009497.1:g.181335G>T
NM_206933.2:c.2332G>T

Protein change:

D778Y

Links:

dbSNP: rs142898216

NCBI 1000 Genomes Browser:

rs142898216

Molecular consequence:

NM_007123.6:c.2332G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_206933.4:c.2332G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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PREDICTED: transmembrane emp24 domain-containing protein p24delta9-like [Cucumis...
PREDICTED: transmembrane emp24 domain-containing protein p24delta9-like [Cucumis melo]
gi|659131580|ref|XP_008465758.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002051125	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Dec 14, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26969326, 25649381, 17085681, 32579692, 32637036, 31736247 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002051125

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Dec 14, 2021)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss.

Sloan-Heggen CM, Bierer AO, Shearer AE, Kolbe DL, Nishimura CJ, Frees KL, Ephraim SS, Shibata SB, Booth KT, Campbell CA, Ranum PT, Weaver AE, Black-Ziegelbein EA, Wang D, Azaiez H, Smith RJH.

Hum Genet. 2016 Apr;135(4):441-450. doi: 10.1007/s00439-016-1648-8. Epub 2016 Mar 11.

PubMed [citation]

PMID:: 26969326
PMCID:: PMC4796320

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Lenassi E, Vincent A, Li Z, Saihan Z, Coffey AJ, Steele-Stallard HB, Moore AT, Steel KP, Luxon LM, Héon E, Bitner-Glindzicz M, Webster AR.

Eur J Hum Genet. 2015 Oct;23(10):1318-27. doi: 10.1038/ejhg.2014.283. Epub 2015 Feb 4.

PubMed [citation]

PMID:: 25649381
PMCID:: PMC4592079

See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002051125.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: USH2A c.2332G>T (p.Asp778Tyr) results in a non-conservative amino acid change located in the Laminin-type EGF domain (IPR002049) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 250894 control chromosomes in the gnomAD database, including 1 homozygote. c.2332G>T has been reported in the literature in multiple compound heterozygous individuals affected with Usher Syndrome or retinal disease (examples: Aller_2006, Sloan-Heggen_2016, Zenteno_2019, and McGowan_2020), as well as a homozygous individual with normal hearing and nyctalopia (Lenassi_2015). These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic (n=3) and as a variant of uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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