NM_206933.4(USH2A):c.5399G>A (p.Trp1800Ter) AND Usher syndrome type 2A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 4, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002272322.4

Allele description [Variation Report for NM_206933.4(USH2A):c.5399G>A (p.Trp1800Ter)]

NM_206933.4(USH2A):c.5399G>A (p.Trp1800Ter)

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.5399G>A (p.Trp1800Ter)

HGVS:

NC_000001.11:g.216078262C>T
NG_009497.2:g.350187G>A
NM_206933.4:c.5399G>AMANE SELECT
NP_996816.3:p.Trp1800Ter
NC_000001.10:g.216251604C>T
NG_009497.1:g.350135G>A
NM_206933.2:c.5399G>A

Protein change:

W1800*

Links:

dbSNP: rs1553299079

NCBI 1000 Genomes Browser:

rs1553299079

Molecular consequence:

NM_206933.4:c.5399G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Usher syndrome type 2A
Synonyms:: USHER SYNDROME, TYPE IIA; RETINAL DISEASE IN USHER SYNDROME TYPE IIA, MODIFIER OF
Identifiers:: MONDO: MONDO:0010169; MedGen: C1848634; Orphanet: 231178; Orphanet: 886; OMIM: 276901

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002556744	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 7, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24944099, 25741868
SCV004181815	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002556744

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 7, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004181815

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 4, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots.

Baux D, Blanchet C, Hamel C, Meunier I, Larrieu L, Faugère V, Vaché C, Castorina P, Puech B, Bonneau D, Malcolm S, Claustres M, Roux AF.

Hum Mutat. 2014 Oct;35(10):1179-86. doi: 10.1002/humu.22608. Epub 2014 Jul 15.

PubMed [citation]

PMID:: 24944099

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Genetics and Molecular Pathology, SA Pathology, SCV002556744.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The USH2A c.5399G>A variant is classified as PATHOGENIC (PVS1, PS4, PM3) The USH2A c.5399G>A variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 1800 (PVS1). The variant has been reported in several individuals with a clinical presentation of Usher syndrome, type 2A (PMID:24944099; 32531858) (PS4). This variant has been detected in trans with another pathogenic variant for this recessive condition in both this individual and in other reported cases in the literature (PM3). This variant is in dbSNP (rs1553299079) and has been reported in population databases (gnomAD 2/152142 allelels, no homozygotes. This variant has been reported in ClinVar as pathogenic for Usher syndrome and retinal dystrophy by other diagnostic laboratories (ClinVar Variation ID: 556449) and as damaging for Usher syndrome 2 in the disease database HGMD (CM149920).

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

From Genome-Nilou Lab, SCV004181815.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 5, 2025

ClinVar

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