NM_004415.4(DSP):c.7820del (p.Ser2607fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 12, 2020
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:: RCV001389705.7

Allele description [Variation Report for NM_004415.4(DSP):c.7820del (p.Ser2607fs)]

NM_004415.4(DSP):c.7820del (p.Ser2607fs)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.7820del (p.Ser2607fs)

HGVS:

NC_000006.12:g.7585082del
NG_008803.1:g.48446del
NM_001008844.3:c.6023del
NM_001319034.2:c.6491del
NM_004415.4:c.7820delMANE SELECT
NP_001008844.1:p.Ser2008fs
NP_001305963.1:p.Ser2164fs
NP_004406.2:p.Ser2607fs
LRG_423:g.48446del
NC_000006.11:g.7585315del

Protein change:

S2008fs

Links:

dbSNP: rs2113703361

NCBI 1000 Genomes Browser:

rs2113703361

Molecular consequence:

NM_001008844.3:c.6023del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319034.2:c.6491del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004415.4:c.7820del - 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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Homo sapiens microtubule interacting and trafficking domain containing 1 (MITD1)...
Homo sapiens microtubule interacting and trafficking domain containing 1 (MITD1), transcript variant 4, mRNA
gi|1676325137|ref|NM_001320419.2|

Nucleotide
CBTC7484.fwd NICHD_XGC_tropBone1 Xenopus tropicalis cDNA clone IMAGE:8939785 5',...
CBTC7484.fwd NICHD_XGC_tropBone1 Xenopus tropicalis cDNA clone IMAGE:8939785 5', mRNA sequence
gi|126270375|gnl|dbEST|45044202|gb| 650.1|

Nucleotide
BJ045732 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clon...
BJ045732 NIBB Mochii normalized Xenopus neurula library Xenopus laevis cDNA clone XL005b13 3', mRNA sequence
gi|17372428|gnl|dbEST|10467704|dbj| 732.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001591156	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 12, 2020)	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

SCV001591156

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 12, 2020)

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, SCV001591156.4

#	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 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. This variant has not been reported in the literature in individuals with DSP-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the DSP gene (p.Ser2607Thrfs*31). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 265 amino acids 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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