U.S. flag

An official website of the United States government

NM_004415.4(DSP):c.7960C>T (p.Gln2654Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 16, 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:
RCV003118502.3

Allele description [Variation Report for NM_004415.4(DSP):c.7960C>T (p.Gln2654Ter)]

NM_004415.4(DSP):c.7960C>T (p.Gln2654Ter)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.7960C>T (p.Gln2654Ter)
HGVS:
  • NC_000006.12:g.7585222C>T
  • NG_008803.1:g.48586C>T
  • NM_001008844.3:c.6163C>T
  • NM_001319034.2:c.6631C>T
  • NM_004415.4:c.7960C>TMANE SELECT
  • NP_001008844.1:p.Gln2055Ter
  • NP_001305963.1:p.Gln2211Ter
  • NP_004406.2:p.Gln2654Ter
  • NP_004406.2:p.Gln2654Ter
  • LRG_423t1:c.7960C>T
  • LRG_423:g.48586C>T
  • LRG_423p1:p.Gln2654Ter
  • NC_000006.11:g.7585455C>T
  • NM_004415.2:c.7960C>T
Protein change:
Q2055*
Molecular consequence:
  • NM_001008844.3:c.6163C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319034.2:c.6631C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004415.4:c.7960C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma
Synonyms:
Palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair; Epidermolytic palmoplantar keratoderma woolly hair and dilated cardiomyopathy; Dilated cardiomyopathy with woolly hair and keratoderma; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011581; MedGen: C1854063; Orphanet: 65282; OMIM: 605676
Name:
Arrhythmogenic right ventricular dysplasia 8 (ARVD8)
Synonyms:
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 8; Arrhythmogenic right ventricular cardiomyopathy, type 8; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 8
Identifiers:
MONDO: MONDO:0011831; MedGen: C1843896; OMIM: 607450

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003786681Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 16, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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, SCV003786681.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change creates a premature translational stop signal (p.Gln2654*) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 218 amino acid(s) of the DSP protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant disrupts a region of the DSP protein in which other variant(s) (p.Glu2728Glyfs*11) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Jun 2, 2024