NM_004415.4(DSP):c.3157A>G (p.Asn1053Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 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:: RCV002638187.3

Allele description [Variation Report for NM_004415.4(DSP):c.3157A>G (p.Asn1053Asp)]

NM_004415.4(DSP):c.3157A>G (p.Asn1053Asp)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.3157A>G (p.Asn1053Asp)

HGVS:

NC_000006.12:g.7579347A>G
NG_008803.1:g.42711A>G
NM_001008844.3:c.3157A>G
NM_001319034.2:c.3157A>G
NM_004415.4:c.3157A>GMANE SELECT
NP_001008844.1:p.Asn1053Asp
NP_001305963.1:p.Asn1053Asp
NP_004406.2:p.Asn1053Asp
NP_004406.2:p.Asn1053Asp
LRG_423t1:c.3157A>G
LRG_423:g.42711A>G
LRG_423p1:p.Asn1053Asp
NC_000006.11:g.7579580A>G
NM_004415.2:c.3157A>G

Protein change:

N1053D

Molecular consequence:

NM_001008844.3:c.3157A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319034.2:c.3157A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004415.4:c.3157A>G - missense variant - [Sequence Ontology: SO:0001583]

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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SUMO-1 specific protease 4 [Mus musculus]
SUMO-1 specific protease 4 [Mus musculus]
gi|159032049|ref|NP_694733.3|

Protein
Mus musculus adult male medulla oblongata cDNA, RIKEN full-length enriched libra...
Mus musculus adult male medulla oblongata cDNA, RIKEN full-length enriched library, clone:6330576B01 product:unclassifiable, full insert sequence
gi|12857876|dbj|AK018254.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003521411	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2022)	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

SCV003521411

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2022)

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, SCV003521411.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1053 of the DSP protein (p.Asn1053Asp).

#	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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