NM_004415.4(DSP):c.5014C>G (p.Gln1672Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 11, 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:: RCV002515256.2

Allele description [Variation Report for NM_004415.4(DSP):c.5014C>G (p.Gln1672Glu)]

NM_004415.4(DSP):c.5014C>G (p.Gln1672Glu)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.5014C>G (p.Gln1672Glu)

HGVS:

NC_000006.12:g.7581204C>G
NG_008803.1:g.44568C>G
NM_001008844.3:c.3582+1432C>G
NM_001319034.2:c.4050+964C>G
NM_004415.4:c.5014C>GMANE SELECT
NP_004406.2:p.Gln1672Glu
LRG_423t1:c.5014C>G
LRG_423:g.44568C>G
NC_000006.11:g.7581437C>G
NM_004415.2:c.5014C>G
NM_004415.3:c.5014C>G

Protein change:

Q1672E

Links:

dbSNP: rs786205416

NCBI 1000 Genomes Browser:

rs786205416

Molecular consequence:

NM_001008844.3:c.3582+1432C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001319034.2:c.4050+964C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_004415.4:c.5014C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003273743	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 11, 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

SCV003273743

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 11, 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, SCV003273743.1

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

Description

This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1672 of the DSP protein (p.Gln1672Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 191640). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.

#	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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