NM_001943.5(DSG2):c.495dup (p.Gly166fs) AND Arrhythmogenic right ventricular dysplasia 10

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 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:: RCV000813935.9

Allele description [Variation Report for NM_001943.5(DSG2):c.495dup (p.Gly166fs)]

NM_001943.5(DSG2):c.495dup (p.Gly166fs)

Gene:

DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.495dup (p.Gly166fs)

HGVS:

NC_000018.10:g.31521215dup
NG_007072.3:g.27974dup
NM_001943.5:c.495dupMANE SELECT
NP_001934.2:p.Gly166fs
LRG_397t1:c.495dup
LRG_397:g.27974dup
NC_000018.9:g.29101176_29101177insT
NC_000018.9:g.29101178dup
NM_001943.3:c.495dup
NM_001943.3:c.495dupT

Protein change:

G166fs

Links:

dbSNP: rs781532110

NCBI 1000 Genomes Browser:

rs781532110

Molecular consequence:

NM_001943.5:c.495dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 10
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular cardiomyopathy, type 10; Arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 10; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012434; MedGen: C1857777; OMIM: 610193

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000954319	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 17, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27532257, 17105751, 31386562, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000954319

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 17, 2022)

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

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

Desmoglein-2 mutations in arrhythmogenic right ventricular cardiomyopathy: a genotype-phenotype characterization of familial disease.

Syrris P, Ward D, Asimaki A, Evans A, Sen-Chowdhry S, Hughes SE, McKenna WJ.

Eur Heart J. 2007 Mar;28(5):581-8. Epub 2006 Nov 14.

PubMed [citation]

PMID:: 17105751

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000954319.6

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280230). This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 27532257). This variant is present in population databases (rs781532110, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Gly166Trpfs*4) in the DSG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG2 are known to be pathogenic (PMID: 17105751, 31386562).

#	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: Feb 20, 2024

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