NM_024422.6(DSC2):c.882dup (p.Phe295fs) AND Arrhythmogenic right ventricular dysplasia 11

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 26, 2017
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:: RCV000462858.6

Allele description [Variation Report for NM_024422.6(DSC2):c.882dup (p.Phe295fs)]

NM_024422.6(DSC2):c.882dup (p.Phe295fs)

Gene:

DSC2:desmocollin 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_024422.6(DSC2):c.882dup (p.Phe295fs)

HGVS:

NC_000018.10:g.31086636dup
NG_008208.2:g.20790dup
NM_004949.5:c.882dup
NM_024422.6:c.882dupMANE SELECT
NP_004940.1:p.Phe295fs
NP_077740.1:p.Phe295fs
LRG_400:g.20790dup
NC_000018.9:g.28666598_28666599insT
NC_000018.9:g.28666599dup
NM_024422.4:c.882dupA

Protein change:

F295fs

Links:

dbSNP: rs1060502989

NCBI 1000 Genomes Browser:

rs1060502989

Molecular consequence:

NM_004949.5:c.882dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024422.6:c.882dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 11
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 11; Arrhythmogenic right ventricular cardiomyopathy, type 11; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy11
Identifiers:: MONDO: MONDO:0012506; MedGen: C1864850; OMIM: 610476

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551486	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 26, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23911551, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551486

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 26, 2017)

germline

clinical testing

PubMed (2)
[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

Mechanistic basis of desmosome-targeted diseases.

Al-Jassar C, Bikker H, Overduin M, Chidgey M.

J Mol Biol. 2013 Nov 1;425(21):4006-22. doi: 10.1016/j.jmb.2013.07.035. Epub 2013 Aug 2. Review.

PubMed [citation]

PMID:: 23911551
PMCID:: PMC3807649

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000551486.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in DSC2 are known to be pathogenic (PMID: 23911551). This sequence change inserts 1 nucleotide in exon 7 of the DSC2 mRNA (c.882dupA), causing a frameshift at codon 295. This creates a premature translational stop signal (p.Phe295Ilefs*23) and is expected to result in an absent or disrupted protein product.

#	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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