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NM_206933.4(USH2A):c.7787A>G (p.Tyr2596Cys) AND Usher syndrome type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 5, 2024
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:
RCV003994275.1

Allele description [Variation Report for NM_206933.4(USH2A):c.7787A>G (p.Tyr2596Cys)]

NM_206933.4(USH2A):c.7787A>G (p.Tyr2596Cys)

Gene:
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.7787A>G (p.Tyr2596Cys)
HGVS:
  • NC_000001.11:g.215888862T>C
  • NG_009497.2:g.539587A>G
  • NM_206933.4:c.7787A>GMANE SELECT
  • NP_996816.3:p.Tyr2596Cys
  • NC_000001.10:g.216062204T>C
  • NG_009497.1:g.539535A>G
  • NM_206933.2:c.7787A>G
Protein change:
Y2596C
Links:
dbSNP: rs371685066
NCBI 1000 Genomes Browser:
rs371685066
Molecular consequence:
  • NM_206933.4:c.7787A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Usher syndrome type 2
Synonyms:
Usher Syndrome, Type II
Identifiers:
MONDO: MONDO:0016484; MedGen: C0339534

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004812519Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 5, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Molecular Genetics, Royal Melbourne Hospital, SCV004812519.1

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

Description

This sequence change in USH2A is predicted to replace tyrosine with cysteine at codon 2596, p.(Tyr2596Cys). The tyrosine residue is moderately conserved (100 vertebrates, Multiz alignments), and is located in the fibronectin type 3 domain. There is a large physicochemical difference between tyrosine and cysteine. The highest population minor allele frequency in the population database gnomAD v2.1 is 0.03% (7/24,956 alleles) in the African/African-American population, which is consistent with recessive disease. To our knowledge, this variant has not been previously reported in the relevant scientific literature. Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.897). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, PP3

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

Last Updated: Sep 29, 2024