NM_024422.6(DSC2):c.34G>A (p.Gly12Arg) AND not specified

Germline classification:: Benign (1 submission)
Last evaluated:: Aug 31, 2020
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:: RCV000181171.5

Allele description [Variation Report for NM_024422.6(DSC2):c.34G>A (p.Gly12Arg)]

NM_024422.6(DSC2):c.34G>A (p.Gly12Arg)

Genes:

DSCAS:DSC1/DSC2 antisense RNA [Gene - HGNC]
DSC2:desmocollin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_024422.6(DSC2):c.34G>A (p.Gly12Arg)

Other names:

p.G12R:GGA>AGA

HGVS:

NC_000018.10:g.31101938C>T
NG_008208.2:g.5488G>A
NM_004949.5:c.34G>A
NM_024422.6:c.34G>AMANE SELECT
NP_004940.1:p.Gly12Arg
NP_077740.1:p.Gly12Arg
LRG_400:g.5488G>A
NC_000018.9:g.28681901C>T
NM_024422.3:c.34G>A
NM_024422.4:c.34G>A

Protein change:

G12R

Links:

dbSNP: rs568391206

NCBI 1000 Genomes Browser:

rs568391206

Molecular consequence:

NM_004949.5:c.34G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024422.6:c.34G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000699499	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Aug 31, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21636032, 25351510 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000699499

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Aug 31, 2020)

germline

clinical testing

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

Citation Link

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

Distinguishing arrhythmogenic right ventricular cardiomyopathy/dysplasia-associated mutations from background genetic noise.

Kapplinger JD, Landstrom AP, Salisbury BA, Callis TE, Pollevick GD, Tester DJ, Cox MG, Bhuiyan Z, Bikker H, Wiesfeld AC, Hauer RN, van Tintelen JP, Jongbloed JD, Calkins H, Judge DP, Wilde AA, Ackerman MJ.

J Am Coll Cardiol. 2011 Jun 7;57(23):2317-27. doi: 10.1016/j.jacc.2010.12.036.

PubMed [citation]

PMID:: 21636032
PMCID:: PMC6311127

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM.

Heart. 2015 Feb;101(4):294-301. doi: 10.1136/heartjnl-2014-306387. Epub 2014 Oct 28.

PubMed [citation]

PMID:: 25351510
PMCID:: PMC4345808

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699499.2

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

Description

Variant summary: DSC2 c.34G>A (p.Gly12Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 123860 control chromosomes. The observed variant frequency is approximately 19 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSC2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. c.34G>A has been reported in the literature in individuals affected with Cardiovascular disease. These reports do not provide unequivocal conclusions about association of the variant with Cardiovascular disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

#	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: Oct 8, 2024

ClinVar

Relating variation to medicine