NM_206933.4(USH2A):c.5581G>A (p.Gly1861Ser) AND Usher syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 14, 2018)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000710326.1

Allele description [Variation Report for NM_206933.4(USH2A):c.5581G>A (p.Gly1861Ser)]

NM_206933.4(USH2A):c.5581G>A (p.Gly1861Ser)

Genes:
USH2A-AS2:USH2A antisense RNA 2 [Gene - HGNC]
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.5581G>A (p.Gly1861Ser)
Other names:
NM_206933.2(USH2A):c.5581G>A(p.Gly1861Ser); NM_206933.2(USH2A):c.5581G>A
HGVS:
  • NC_000001.11:g.216073292C>T
  • NG_009497.1:g.355105G>A
  • NG_009497.2:g.355157G>A
  • NM_206933.4:c.5581G>AMANE SELECT
  • NP_996816.3:p.Gly1861Ser
  • NC_000001.10:g.216246634C>T
  • NM_206933.2:c.5581G>A
  • O75445:p.Gly1861Ser
  • c.5581G>A
Protein change:
G1861S
Links:
UniProtKB: O75445#VAR_072008; dbSNP: rs375668376
NCBI 1000 Genomes Browser:
rs375668376
Molecular consequence:
  • NM_206933.4:c.5581G>A - 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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000840514ClinGen Hearing Loss Variant Curation Expert Panelreviewed by expert panel
Pathogenic
(Sep 14, 2018)
germlinecuration

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Targeted exome sequencing identified novel USH2A mutations in Usher syndrome families.

Huang XF, Xiang P, Chen J, Xing DJ, Huang N, Min Q, Gu F, Tong Y, Pang CP, Qu J, Jin ZB.

PLoS One. 2013 May 30;8(5):e63832. doi: 10.1371/journal.pone.0063832. Print 2013.

PubMed [citation]
PMID:
23737954
PMCID:
PMC3667821

Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients.

Jiang L, Liang X, Li Y, Wang J, Zaneveld JE, Wang H, Xu S, Wang K, Wang B, Chen R, Sui R.

Orphanet J Rare Dis. 2015 Sep 4;10:110. doi: 10.1186/s13023-015-0329-3.

PubMed [citation]
PMID:
26338283
PMCID:
PMC4559966
See all PubMed Citations (4)

Details of each submission

From ClinGen Hearing Loss Variant Curation Expert Panel, SCV000840514.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (4)

Description

The allele frequency of the p.Gly1861Ser variant in USH2A is 0.017% (3/17184) of East Asian 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_P). This variant was found to have a statistically higher prevalence in affected individuals over controls (PS4; PMIDs: 26310143, 26338283, 23737954, Partners LMM internal data SCV000065557.5). This variant has been detected in 4 patients with hearing loss in trans with pathogenic or suspected-pathogenic variants (PM3_S; PMIDs: 26310143, 26338283, 23737954, Partners LMM internal data SCV000065557.5). The variant has been reported to segregate with hearing loss in one affected family member (PP1, PMID: 26310143). At least one patient with a variant in this gene displayed features of mild to severe hearing loss and retinitis pigmentosa (PP4; PMID: PMIDs: 26310143, 26338283, 23737954, Partners LMM internal data SCV000065557.5). Computational prediction tools and conservation analysis suggest that the p.Gly1861Ser variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PS4, PM2_P, PP3, PM3_S, PP1, PP4.

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

Last Updated: Nov 27, 2021

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