NM_206933.4(USH2A):c.5516T>A (p.Val1839Glu) AND Usher syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 18, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV001171534.2

Allele description [Variation Report for NM_206933.4(USH2A):c.5516T>A (p.Val1839Glu)]

NM_206933.4(USH2A):c.5516T>A (p.Val1839Glu)

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.5516T>A (p.Val1839Glu)
HGVS:
  • NC_000001.11:g.216078145A>T
  • NG_009497.2:g.350304T>A
  • NM_206933.4:c.5516T>AMANE SELECT
  • NP_996816.3:p.Val1839Glu
  • NC_000001.10:g.216251487A>T
  • NG_009497.1:g.350252T>A
  • NM_206933.1:c.5516T>A
  • NM_206933.2:c.5516T>A
  • NM_206933.3(USH2A):c.5516T>A
  • p.Val1839Glu
Protein change:
V1839E
Links:
dbSNP: rs886039867
NCBI 1000 Genomes Browser:
rs886039867
Molecular consequence:
  • NM_206933.4:c.5516T>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001334319ClinGen Hearing Loss Variant Curation Expert Panel
reviewed by expert panel

(Clingen Hl Acmg Specifications Cdh23 Coch Gjb2 Kcnq4 Myo6 Myo7a Slc26a4 Tecta Ush2a V2)		Likely pathogenic
(Oct 18, 2023) 		germlinecuration

Citation Link

Help

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, SCV001334319.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.5516T>A variant in USH2A is a missense variant predicted to cause substitution of valine to glutamate at amino acid position 1839. The variant was absent from gnomAD v2.1.1 and present in 0.001549% (1/64578) of non-Finnish European chromosomes in gnomAD v3 (PM2_Supporting). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. This variant has been detected in at least 4 individuals (2 with Usher syndrome and 2 with isolated retinitis pigmentosa) (total of 2.5 PM3 points, PM3_Strong). One individual with Usher syndrome was assumed to be compound heterozygous with a pathogenic c.2299del variant, but phase unknown (VCV000002351.78; PMID: 26927203). The other two individuals had retinitis pigmentosa and were assumed compound heterozygous with pathogenic p.(Cys759Phe) variant (VCV000002356.89; PMID: 26927203; PMID: 34203967). One patient displayed both retinal degradation and sensorineural hearing loss, features highly specific for USH2A (PP4). Patients with this variant may present with either Usher syndrome or with isolated RP. Isolated RP presentations are more common when the variant is seen with missense variants while Usher syndrome is more common when it is found with truncating variants. In summary, the clinical significance of this variant is likely pathogenic. ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss Expert Panel: PM2_Supporting, PM3_Strong, PP4 (VCEP specifications version 2; 10.18.2023).

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

Last Updated: Jun 23, 2024