NM_206933.4(USH2A):c.820C>G (p.Arg274Gly) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 29, 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:: RCV001360100.7

Allele description [Variation Report for NM_206933.4(USH2A):c.820C>G (p.Arg274Gly)]

NM_206933.4(USH2A):c.820C>G (p.Arg274Gly)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.820C>G (p.Arg274Gly)

HGVS:

NC_000001.11:g.216327619G>C
NG_009497.2:g.100830C>G
NM_007123.6:c.820C>G
NM_206933.4:c.820C>GMANE SELECT
NP_009054.6:p.Arg274Gly
NP_996816.3:p.Arg274Gly
NC_000001.10:g.216500961G>C
NG_009497.1:g.100778C>G
NM_206933.2:c.820C>G

Protein change:

R274G

Links:

dbSNP: rs397518036

NCBI 1000 Genomes Browser:

rs397518036

Molecular consequence:

NM_007123.6:c.820C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_206933.4:c.820C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001556000	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27460420, 28041643, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001556000

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 29, 2022)

germline

clinical testing

PubMed (3)
[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

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

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]

PMID:: 28041643
PMCID:: PMC5223092

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001556000.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg274 amino acid residue in USH2A. Other variant(s) that disrupt this residue have been observed in individuals with USH2A-related conditions (PMID: 27460420), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 438026). This missense change has been observed in individual(s) with clinical features of Usher syndrome (PMID: 28041643; Invitae). This variant is present in population databases (rs397518036, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 274 of the USH2A protein (p.Arg274Gly).

#	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: Sep 29, 2024

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