NM_024422.6(DSC2):c.2112_2116del (p.Phe708fs) AND Arrhythmogenic right ventricular dysplasia 11

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 11, 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:: RCV002529804.2

Allele description [Variation Report for NM_024422.6(DSC2):c.2112_2116del (p.Phe708fs)]

NM_024422.6(DSC2):c.2112_2116del (p.Phe708fs)

Gene:

DSC2:desmocollin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_024422.6(DSC2):c.2112_2116del (p.Phe708fs)

HGVS:

NC_000018.10:g.31071618_31071622del
NG_008208.2:g.35808_35812del
NM_004949.5:c.2112_2116del
NM_024422.6:c.2112_2116delMANE SELECT
NP_004940.1:p.Phe708fs
NP_077740.1:p.Phe708fs
LRG_400:g.35808_35812del
NC_000018.9:g.28651580_28651584del
NC_000018.9:g.28651584_28651588del
NM_024422.4:c.2112_2116delAGCAT

Protein change:

F708fs

Links:

dbSNP: rs1555637555

NCBI 1000 Genomes Browser:

rs1555637555

Molecular consequence:

NM_004949.5:c.2112_2116del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024422.6:c.2112_2116del - 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
SCV003007557	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 11, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33258288, 23911551, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003007557

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 11, 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

Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases.

Quaio CRDC, Moreira CM, Novo-Filho GM, Sacramento-Bobotis PR, Groenner Penna M, Perazzio SF, Dutra AP, da Silva RA, Santos MNP, de Arruda VYN, Freitas VG, Pereira VC, Pintao MC, Fornari ARDS, Buzolin AL, Oku AY, Burger M, Ramalho RF, Marco Antonio DS, E Ferreira EN, Pereira OJE, Cantagalli VD, et al.

Am J Med Genet C Semin Med Genet. 2020 Dec;184(4):955-964. doi: 10.1002/ajmg.c.31860. Epub 2020 Nov 30.

PubMed [citation]

PMID:: 33258288

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

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003007557.2

#	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. ClinVar contains an entry for this variant (Variation ID: 523695). This premature translational stop signal has been observed in individual(s) with arrhythmogenic cardiomyopathy (PMID: 33258288). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe708Hisfs*14) in the DSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSC2 are known to be pathogenic (PMID: 23911551).

#	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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