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NM_004415.4(DSP):c.7915C>T (p.Arg2639Trp) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jun 29, 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:
RCV000786122.2

Allele description [Variation Report for NM_004415.4(DSP):c.7915C>T (p.Arg2639Trp)]

NM_004415.4(DSP):c.7915C>T (p.Arg2639Trp)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.7915C>T (p.Arg2639Trp)
HGVS:
  • NC_000006.12:g.7585177C>T
  • NG_008803.1:g.48541C>T
  • NM_001008844.3:c.6118C>T
  • NM_001319034.2:c.6586C>T
  • NM_004415.4:c.7915C>TMANE SELECT
  • NP_001008844.1:p.Arg2040Trp
  • NP_001305963.1:p.Arg2196Trp
  • NP_004406.2:p.Arg2639Trp
  • LRG_423t1:c.7915C>T
  • LRG_423:g.48541C>T
  • NC_000006.11:g.7585410C>T
  • NM_004415.2:c.7915C>T
Protein change:
R2040W
Links:
dbSNP: rs771553674
NCBI 1000 Genomes Browser:
rs771553674
Molecular consequence:
  • NM_001008844.3:c.6118C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001319034.2:c.6586C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004415.4:c.7915C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000924784Stanford Center for Inherited Cardiovascular Disease, Stanford University
no assertion criteria provided
Uncertain significance
(Feb 6, 2017) 		germlineprovider interpretation

SCV002817629GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Jun 29, 2022) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedprovider interpretation

Details of each submission

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000924784.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedprovider interpretationnot provided

Description

Testing was performed by Invitae. Given the lack of case data and presence in population databases, we consider this variant a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has been seen in at least 1 unrelated cases of ARVC (not including this patient's family). There have been no reports of this variant in cases of LVNC or left ventricular systolic dysfunction. The case data is weak. Fressart et al. (2010) report this variant in one of their index patients with ARVC. Patients were recruited in France and Switzerland. They classify it as a variant of uncertain significance but note that it had previously been reported as a mutation in Yu et al. (2008). However, it isn't completely clear that these are referring to the same variant. Yu et al. reports the DSP variant as c.7516G>A (p.Arg2339Gln) in one individual who did not meet criteria for ARVC, but who did have sustained VT, dilation of the RV and non-specific dysfunction of the RV. The transcript used in this paper is reported as the same transcript listed above. This is not the same c. or p. nomenclature. It seems likely that these are not, in fact, the same variant. In silico prediction models to not agree on the effect of this variant. There variant has been seen in 11 of 141,023 individuals listed in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. The variant was specifically in 9 of 63,156 European individuals (MAF=0.007%) and 2 of 15,444 South Asian individuals (MAF=0.006%). Phenotypic information on these individuals is not publicly available.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV002817629.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20400443)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 2, 2024