U.S. flag

An official website of the United States government

NM_206933.4(USH2A):c.10834G>A (p.Val3612Ile) AND Usher syndrome type 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 3, 2022
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:
RCV003994234.1

Allele description [Variation Report for NM_206933.4(USH2A):c.10834G>A (p.Val3612Ile)]

NM_206933.4(USH2A):c.10834G>A (p.Val3612Ile)

Gene:
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.10834G>A (p.Val3612Ile)
HGVS:
  • NC_000001.11:g.215779948C>T
  • NG_009497.2:g.648501G>A
  • NM_206933.4:c.10834G>AMANE SELECT
  • NP_996816.3:p.Val3612Ile
  • NC_000001.10:g.215953290C>T
  • NC_000001.10:g.215953290C>T
  • NG_009497.1:g.648449G>A
  • NM_206933.2:c.10834G>A
Protein change:
V3612I
Links:
dbSNP: rs763125604
NCBI 1000 Genomes Browser:
rs763125604
Molecular consequence:
  • NM_206933.4:c.10834G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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
SCV004812492Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 3, 2022) 		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, SCV004812492.1

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

Description

This sequence change in USH2A is predicted to replace valine with isoleucine at codon 3612, p.(Val3612Ile). The valine residue is weakly conserved (100 vertebrates, UCSC), and is located in the fibronectin type-III 21 domain. There is a small physicochemical difference between valine and isoleucine. The highest population minor allele frequency in gnomAD v2.1 is 0.004% (1/24,964 alleles) in the African/African American population, which is conistent with recessive disease. To our knowledge, this variant has not been reported in the literature in any individuals with USH2A-related disease. The variant has been reported as a variant of uncertain significance (ClinVar ID: 941952). Multiple lines of computational evidence predict a benign effect for the missense substitution (6/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, BP4.

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

Last Updated: Sep 29, 2024