NM_206933.4(USH2A):c.14020A>G (p.Arg4674Gly) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Aug 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001379272.1

Allele description [Variation Report for NM_206933.4(USH2A):c.14020A>G (p.Arg4674Gly)]

NM_206933.4(USH2A):c.14020A>G (p.Arg4674Gly)

Gene:
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.14020A>G (p.Arg4674Gly)
HGVS:
  • NC_000001.11:g.215671085T>C
  • NG_009497.1:g.757312A>G
  • NG_009497.2:g.757364A>G
  • NM_206933.4:c.14020A>GMANE SELECT
  • NP_996816.3:p.Arg4674Gly
  • NC_000001.10:g.215844427T>C
  • NM_206933.2:c.14020A>G
  • O75445:p.Arg4674Gly
Protein change:
R4674G; ARG4674GLY
Links:
UniProtKB: O75445#VAR_038369; OMIM: 608400.0012; dbSNP: rs80338904
NCBI 1000 Genomes Browser:
rs80338904
Molecular consequence:
  • NM_206933.4:c.14020A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001577043Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 8, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.

Kaiserman N, Obolensky A, Banin E, Sharon D.

Arch Ophthalmol. 2007 Feb;125(2):219-24. Erratum in: Arch Ophthalmol. 2007 Aug;125(8):1013.

PubMed [citation]
PMID:
17296898

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001577043.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with glycine at codon 4674 of the USH2A protein (p.Arg4674Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 17296898). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2362). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 20, 2021

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