NM_004415.4(DSP):c.1138C>T (p.Gln380Ter) AND Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 23, 2023
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:: RCV004011622.2

Allele description [Variation Report for NM_004415.4(DSP):c.1138C>T (p.Gln380Ter)]

NM_004415.4(DSP):c.1138C>T (p.Gln380Ter)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.1138C>T (p.Gln380Ter)

HGVS:

NC_000006.12:g.7567447C>T
NG_008803.1:g.30811C>T
NM_001008844.3:c.1138C>T
NM_001319034.2:c.1138C>T
NM_001406591.1:c.1138C>T
NM_004415.4:c.1138C>TMANE SELECT
NP_001008844.1:p.Gln380Ter
NP_001305963.1:p.Gln380Ter
NP_001393520.1:p.Gln380Ter
NP_004406.2:p.Gln380Ter
NP_004406.2:p.Gln380Ter
LRG_423t1:c.1138C>T
LRG_423:g.30811C>T
LRG_423p1:p.Gln380Ter
NC_000006.11:g.7567680C>T
NM_004415.2:c.1138C>T

Protein change:

Q380*

Molecular consequence:

NM_001008844.3:c.1138C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001319034.2:c.1138C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001406591.1:c.1138C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004415.4:c.1138C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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

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Ifnlr1 interferon lambda receptor 1 [Mus musculus]
Ifnlr1 interferon lambda receptor 1 [Mus musculus]
Gene ID:242700

Gene
242700[uid] AND (alive[prop]) (1)
Gene
zp3a.2 zona pellucida glycoprotein 3a, tandem duplicate 2 [Danio rerio]
zp3a.2 zona pellucida glycoprotein 3a, tandem duplicate 2 [Danio rerio]
Gene ID:558677

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004841352	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Oct 23, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31397097, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004841352

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Oct 23, 2023)

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	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Clinical implications of sarcomere and nonsarcomere gene variants in patients with left ventricular noncompaction cardiomyopathy.

Li S, Zhang C, Liu N, Bai H, Hou C, Pu J.

Mol Genet Genomic Med. 2019 Sep;7(9):e874. doi: 10.1002/mgg3.874. Epub 2019 Aug 9.

PubMed [citation]

PMID:: 31397097
PMCID:: PMC6732340

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004841352.1

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

Description

This variant changes 1 nucleotide in exon 9 of the DSP gene and is expected to introduce a premature translation stop signal at codon 380. In addition, splice site prediction tools indicate that this variant may disrupt splicing at intron 9 splice donor site. To our knowledge, protein and RNA functional studies have not been reported for this variant, and its exact molecular consequence is not certain. This variant has been reported in an individual affected with left ventricular non-compaction and dilated cardiomyopathy (PMID: 31397097). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of DSP function is a known mechanism of disease (clinicalgenome.org), and this variant is likely to result in the loss of DSP function. Based on the available evidence, this variant is classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Jun 2, 2024

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