NM_001943.5(DSG2):c.3295A>G (p.Thr1099Ala) AND multiple conditions

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 26, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV002496585.3

Allele description [Variation Report for NM_001943.5(DSG2):c.3295A>G (p.Thr1099Ala)]

NM_001943.5(DSG2):c.3295A>G (p.Thr1099Ala)

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.3295A>G (p.Thr1099Ala)

HGVS:

NC_000018.10:g.31546681A>G
NG_007072.3:g.53440A>G
NM_001943.5:c.3295A>GMANE SELECT
NP_001934.2:p.Thr1099Ala
LRG_397t1:c.3295A>G
LRG_397:g.53440A>G
NC_000018.9:g.29126644A>G
NM_001943.3:c.3295A>G
NM_001943.4:c.3295A>G
c.3295A>G

Protein change:

T1099A

Links:

dbSNP: rs79068489

NCBI 1000 Genomes Browser:

rs79068489

Molecular consequence:

NM_001943.5:c.3295A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 10
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 10; Arrhythmogenic right ventricular cardiomyopathy, type 10; Arrhythmogenic right ventricular dysplasia/cardiomyopathy, type 10; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012434; MedGen: C1857777; OMIM: 610193

Name:: Dilated cardiomyopathy 1BB (CMD1BB)
Synonyms:: CARDIOMYOPATHY, DILATED, 1BB, SUSCEPTIBILITY TO
Identifiers:: MONDO: MONDO:0013030; MedGen: C2752072; Orphanet: 154; OMIM: 612877

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002811410	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Oct 26, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003919891	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2021)	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

SCV002811410

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Oct 26, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003919891

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2021)

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV002811410.1

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

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

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003919891.1

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

Description

DSG2 NM_001943.4 exon 15 p.Thr1099Ala (c.3295A>G): This variant has not been reported in the literature and is present in 0.4% (98/24186) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/18-29126644-A-G). This variant is also present in ClinVar, with several labs classifying this variant as benign or likely benign (Variation ID:44314). This variant amino acid Alanine (Ala) is present in several species including multiple mammals, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign.

#	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: May 12, 2024

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