NM_004415.4(DSP):c.7873dup (p.Thr2625fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 4, 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:: RCV003765112.2

Allele description [Variation Report for NM_004415.4(DSP):c.7873dup (p.Thr2625fs)]

NM_004415.4(DSP):c.7873dup (p.Thr2625fs)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.7873dup (p.Thr2625fs)

HGVS:

NC_000006.12:g.7585135dup
NG_008803.1:g.48499dup
NM_001008844.3:c.6076dup
NM_001319034.2:c.6544dup
NM_004415.4:c.7873dupMANE SELECT
NP_001008844.1:p.Thr2026fs
NP_001305963.1:p.Thr2182fs
NP_004406.2:p.Thr2625fs
LRG_423t1:c.7873dup
LRG_423:g.48499dup
NC_000006.11:g.7585367_7585368insA
NC_000006.11:g.7585368dup
NM_004415.2:c.7873dup
NM_004415.2:c.7873dupA
p.T2625NfsX19

Protein change:

T2026fs

Links:

dbSNP: rs794728149

NCBI 1000 Genomes Browser:

rs794728149

Molecular consequence:

NM_001008844.3:c.6076dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319034.2:c.6544dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004415.4:c.7873dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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semaphorin-6D isoform Sema6D-6 precursor [Mus musculus]
semaphorin-6D isoform Sema6D-6 precursor [Mus musculus]
gi|40385877|ref|NP_954710.1|

Protein
Ligustrum[orgn] (0)
GEO DataSets
Aechmea moorei AND (alive[prop]) (0)
Gene
LRG_273t1 (0)
Nucleotide
ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, partial (chloropl...
ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, partial (chloroplast) [Erucastrum gallicum]
gi|1009024849|gb|AMR44352.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004595146	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004595146

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 4, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004595146.1

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

Description

For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 199928). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr2625Asnfs*19) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 247 amino acid(s) of the DSP protein.

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

Last Updated: Sep 29, 2024

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