NM_024422.6(DSC2):c.23G>T (p.Gly8Val) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 10, 2018
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:: RCV000825917.4

Allele description [Variation Report for NM_024422.6(DSC2):c.23G>T (p.Gly8Val)]

NM_024422.6(DSC2):c.23G>T (p.Gly8Val)

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.23G>T (p.Gly8Val)

Other names:

p.G8V:GGC>GTC; p.Gly8Val

HGVS:

NC_000018.10:g.31101949C>A
NG_008208.2:g.5477G>T
NM_004949.5:c.23G>T
NM_024422.6:c.23G>TMANE SELECT
NP_004940.1:p.Gly8Val
NP_077740.1:p.Gly8Val
LRG_400:g.5477G>T
NC_000018.9:g.28681912C>A
NM_024422.3:c.23G>T
NM_024422.4:c.23G>T

Protein change:

G8V

Links:

dbSNP: rs794728063

NCBI 1000 Genomes Browser:

rs794728063

Molecular consequence:

NM_004949.5:c.23G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024422.6:c.23G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000967402	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Oct 10, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24704780, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967402

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Oct 10, 2018)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis.

Rasmussen TB, Nissen PH, Palmfeldt J, Gehmlich K, Dalager S, Jensen UB, Kim WY, Heickendorff L, Mølgaard H, Jensen HK, Baandrup UT, Bross P, Mogensen J.

Circ Cardiovasc Genet. 2014 Jun;7(3):230-40. doi: 10.1161/CIRCGENETICS.113.000338. Epub 2014 Apr 4.

PubMed [citation]

PMID:: 24704780

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967402.1

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

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Gly8Val varia nt in DSC2 has been reported in 1 individuals with arrhythmogenic cardiomyopathy or borderline arrhythmogenic cardiomyopathy (Rasmussen 2014). It has also been identified in 0.02% (13/57888) of European chromosomes by gnomAD (http://gnomad. broadinstitute.org). Computational prediction tools and conservation analysis su ggest that this variant may not impact the protein, though this information is n ot predictive enough to rule out pathogenicity. In summary, while the clinical s ignificance of the p.Gly8Val variant is uncertain, its frequency suggests that i t is more likely to be benign. ACMG/AMP criteria applied: BP4.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Sep 29, 2024

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