NM_206933.4(USH2A):c.15496A>G (p.Ile5166Val) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 27, 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:: RCV002513599.10

Allele description [Variation Report for NM_206933.4(USH2A):c.15496A>G (p.Ile5166Val)]

NM_206933.4(USH2A):c.15496A>G (p.Ile5166Val)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.15496A>G (p.Ile5166Val)

HGVS:

NC_000001.11:g.215628837T>C
NG_009497.2:g.799612A>G
NM_206933.4:c.15496A>GMANE SELECT
NP_996816.3:p.Ile5166Val
NC_000001.10:g.215802179T>C
NG_009497.1:g.799560A>G
NM_206933.2:c.15496A>G
NM_206933.3:c.15496A>G
c.15496A>G

Protein change:

I5166V

Links:

dbSNP: rs111033419

NCBI 1000 Genomes Browser:

rs111033419

Molecular consequence:

NM_206933.4:c.15496A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Ulp1-like peptidase [Cucumis melo var. makuwa]
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gi|1731034751|gb|TYK22555.1||gnl|WG D|E5676_scaffold584G00100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003522993	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26969326, 27460420, 32531858, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003522993

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss.

Sloan-Heggen CM, Bierer AO, Shearer AE, Kolbe DL, Nishimura CJ, Frees KL, Ephraim SS, Shibata SB, Booth KT, Campbell CA, Ranum PT, Weaver AE, Black-Ziegelbein EA, Wang D, Azaiez H, Smith RJH.

Hum Genet. 2016 Apr;135(4):441-450. doi: 10.1007/s00439-016-1648-8. Epub 2016 Mar 11.

PubMed [citation]

PMID:: 26969326
PMCID:: PMC4796320

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C, Lefèvre GM, Hardelin JP, El-Amraoui A, Singh-Estivalet A, Mohand-Saïd S, Kohl S, Kurtenbach A, Sliesoraityte I, Zobor D, Gherbi S, Testa F, Simonelli F, Banfi S, Fakin A, Glavač D, Jarc-Vidmar M, et al.

Eur J Hum Genet. 2016 Dec;24(12):1730-1738. doi: 10.1038/ejhg.2016.99. Epub 2016 Jul 27.

PubMed [citation]

PMID:: 27460420
PMCID:: PMC5117943

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003522993.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 5166 of the USH2A protein (p.Ile5166Val). This variant is present in population databases (rs111033419, gnomAD 0.009%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 26969326, 27460420, 32531858). ClinVar contains an entry for this variant (Variation ID: 48465). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt USH2A protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 10, 2024

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