NM_001943.5(DSG2):c.3233G>C (p.Gly1078Ala) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 4, 2018
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:: RCV000757181.9

Allele description [Variation Report for NM_001943.5(DSG2):c.3233G>C (p.Gly1078Ala)]

NM_001943.5(DSG2):c.3233G>C (p.Gly1078Ala)

Genes:

DSG2-AS1:DSG2 antisense RNA 1 [Gene - HGNC]
DSG2:desmoglein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001943.5(DSG2):c.3233G>C (p.Gly1078Ala)

HGVS:

NC_000018.10:g.31546619G>C
NG_007072.3:g.53378G>C
NM_001943.5:c.3233G>CMANE SELECT
NP_001934.2:p.Gly1078Ala
LRG_397t1:c.3233G>C
LRG_397:g.53378G>C
NC_000018.9:g.29126582G>C
NM_001943.3:c.3233G>C

Protein change:

G1078A

Links:

dbSNP: rs1064795829

NCBI 1000 Genomes Browser:

rs1064795829

Molecular consequence:

NM_001943.5:c.3233G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000572009	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Oct 24, 2016)	germline	clinical testing	Citation Link,
SCV000885317	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (May 4, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000572009

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Oct 24, 2016)

germline

clinical testing

Citation Link,

SCV000885317

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(May 4, 2018)

germline

clinical testing

Citation Link

Help

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 GeneDx, SCV000572009.3

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

Description

A variant of uncertain significance has been identified in the DSG2 gene. The G1078A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G1078A variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the G1078A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and this substitution occurs at a position that is not conserved across species. Lastly, in silico analysis predicts this variant likely does not alter the protein structure/function.

#	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 ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000885317.1

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

Description

The DSG2 c.3233G>C; p.Gly1078Ala variant (ClinVar variant ID 422516), 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 0.0004% (identified on 1 out of 246,030 chromosomes). The glycine at position 1078 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Gly1078Ala 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.Gly1078Ala 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

Last Updated: Jan 13, 2025

ClinVar

Relating variation to medicine