NM_001943.5(DSG2):c.2536G>T (p.Asp846Tyr) AND Arrhythmogenic right ventricular cardiomyopathy, type 10

Clinical significance:Uncertain significance (Last evaluated: May 7, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000559043.2

Allele description [Variation Report for NM_001943.5(DSG2):c.2536G>T (p.Asp846Tyr)]

NM_001943.5(DSG2):c.2536G>T (p.Asp846Tyr)

Genes:
DSG2-AS1:DSG2 antisense RNA 1 [Gene - HGNC]
DSG2:desmoglein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q12.1
Genomic location:
Preferred name:
NM_001943.5(DSG2):c.2536G>T (p.Asp846Tyr)
HGVS:
  • NC_000018.10:g.31545922G>T
  • NG_007072.3:g.52681G>T
  • NM_001943.5:c.2536G>TMANE SELECT
  • NP_001934.2:p.Asp846Tyr
  • LRG_397t1:c.2536G>T
  • LRG_397:g.52681G>T
  • NC_000018.9:g.29125885G>T
  • NM_001943.3:c.2536G>T
Protein change:
D846Y
Links:
dbSNP: rs1226243364
NCBI 1000 Genomes Browser:
rs1226243364
Molecular consequence:
  • NM_001943.5:c.2536G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy, type 10 (ARVD10)
Synonyms:
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular dysplasia type 10; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy10
Identifiers:
MONDO: MONDO:0012434; MedGen: C1857777; OMIM: 610193

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000641974Invitaecriteria provided, single submitter
Uncertain significance
(May 7, 2019)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

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, SCV000641974.3

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

Description

This sequence change replaces aspartic acid with tyrosine at codon 846 of the DSG2 protein (p.Asp846Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a DSG2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C1). In summary, this variant has uncertain impact on DSG2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 5

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

Last Updated: Mar 14, 2021

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