NM_004415.4(DSP):c.7570_7573del (p.Thr2524fs) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jul 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001381245.1

Allele description [Variation Report for NM_004415.4(DSP):c.7570_7573del (p.Thr2524fs)]

NM_004415.4(DSP):c.7570_7573del (p.Thr2524fs)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.7570_7573del (p.Thr2524fs)
HGVS:
  • NC_000006.12:g.7584832_7584835del
  • NG_008803.1:g.48196_48199del
  • NM_001008844.3:c.5773_5776del
  • NM_001319034.2:c.6241_6244del
  • NM_004415.4:c.7570_7573delMANE SELECT
  • NP_001008844.1:p.Thr1925fs
  • NP_001305963.1:p.Thr2081fs
  • NP_004406.2:p.Thr2524fs
  • LRG_423:g.48196_48199del
  • NC_000006.11:g.7585063_7585066del
  • NC_000006.11:g.7585065_7585068del
Protein change:
T1925fs
Links:
dbSNP: rs1561703922
NCBI 1000 Genomes Browser:
rs1561703922
Molecular consequence:
  • NM_001008844.3:c.5773_5776del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001319034.2:c.6241_6244del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004415.4:c.7570_7573del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Dilated cardiomyopathy with woolly hair and keratoderma (DCWHK)
Synonyms:
Palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair; Epidermolytic palmoplantar keratoderma woolly hair and dilated cardiomyopathy; Carvajal syndrome
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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001579564Invitaecriteria provided, single submitter
Pathogenic
(Jul 15, 2020)
germlineclinical testing

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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001579564.1

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

Description

This sequence change results in a premature translational stop signal in the DSP gene (p.Thr2524Alafs*36). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 348 amino acids of the DSP protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 560379). This variant disrupts the C-terminus of the DSP protein. Other variant(s) that disrupt this region (p.Glu2728Glyfs*11) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. 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: Oct 7, 2021

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