NM_002230.4(JUP):c.1982G>A (p.Arg661Gln) AND not provided

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Sep 19, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000757415.16

Allele description [Variation Report for NM_002230.4(JUP):c.1982G>A (p.Arg661Gln)]

NM_002230.4(JUP):c.1982G>A (p.Arg661Gln)

Gene:

JUP:junction plakoglobin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_002230.4(JUP):c.1982G>A (p.Arg661Gln)

HGVS:

NC_000017.11:g.41757479C>T
NG_009090.2:g.34234G>A
NM_001352773.2:c.1982G>A
NM_001352774.2:c.1982G>A
NM_001352775.2:c.1982G>A
NM_001352776.2:c.1982G>A
NM_001352777.2:c.1982G>A
NM_002230.4:c.1982G>AMANE SELECT
NM_021991.4:c.1982G>A
NP_001339702.1:p.Arg661Gln
NP_001339703.1:p.Arg661Gln
NP_001339704.1:p.Arg661Gln
NP_001339705.1:p.Arg661Gln
NP_001339706.1:p.Arg661Gln
NP_002221.1:p.Arg661Gln
NP_068831.1:p.Arg661Gln
LRG_401t2:c.1982G>A
LRG_401:g.34234G>A
NC_000017.10:g.39913731C>T
NM_002230.2:c.1982G>A

Protein change:

R661Q

Links:

dbSNP: rs555499592

NCBI 1000 Genomes Browser:

rs555499592

Molecular consequence:

NM_001352773.2:c.1982G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352774.2:c.1982G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352775.2:c.1982G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352776.2:c.1982G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352777.2:c.1982G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002230.4:c.1982G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021991.4:c.1982G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000885624	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Apr 20, 2018)	germline	clinical testing	Citation Link,
SCV001742391	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001958095	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002575876	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 19, 2022)	germline	clinical testing	Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885624.1

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

Description

The JUP c.1982G>A; p.Arg661Gln variant (rs555499592, ClinVar variant ID 409985), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.1% (identified on 27 out of 18,870 chromosomes). The arginine at position 661 is moderately conserved, considering 13 species, and computational analyses of the effects of the p.Arg661Gln variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Arg661Gln variant cannot be determined with certainty.

#	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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001742391.3

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

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001958095.1

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

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

From GeneDx, SCV002575876.2

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Has been reported in association with dilated cardiomyopathy (Verdonschot et al., 2020); This variant is associated with the following publications: (PMID: 32880476)

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

Last Updated: Jan 13, 2025

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