rs55657337

Variant names:

• chr18-31521267-T-A
• rs55657337
• NM_001943.5:c.523+24T>A

Your query was ambiguous. Multiple possible variants found:

• chr18-31521267-T-A
• chr18-31521267-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001943.5(DSG2):​c.523+24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,533,416 control chromosomes in the GnomAD database, including 8,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2174 hom., cov: 31)
  • Exomes 𝑓: 0.10 (6270 hom.)
• Consequence: DSG2 NM_001943.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.03
• Publications: 3 publications found

Genes affected

DSG2 (HGNC:3049): (desmoglein 2) This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. Mutations in this gene have been associated with arrhythmogenic right ventricular dysplasia, familial, 10. [provided by RefSeq, Jan 2016]

DSG2 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• arrhythmogenic right ventricular dysplasia 10

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy 1BB

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-31521267-T-A is Benign according to our data. Variant chr18-31521267-T-A is described in ClinVar as Benign. ClinVar VariationId is 188447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001943.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG2	NM_001943.5	MANE Select	c.523+24T>A		intron	N/A	NP_001934.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG2	ENST00000261590.13	TSL:1 MANE Select	c.523+24T>A		intron	N/A	ENSP00000261590.8
	DSG2	ENST00000684461.1		n.378T>A		non_coding_transcript_exon	Exon 3 of 3
	DSG2	ENST00000713817.1		c.514+24T>A		intron	N/A	ENSP00000519121.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22543 AN: 151174 Hom.: 2165 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.152

GnomAD2 exomes AF: 0.0968 AC: 21021 AN: 217070 AF XY: 0.0960

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0566

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.0352

Gnomad FIN exome AF: 0.0700

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.104 AC: 143978 AN: 1382134 Hom.: 6270 Cov.: 32 AF XY: 0.103 AC XY: 71051 AN XY: 689098

African (AFR) AF: 0.267 AC: 8016 AN: 30020

American (AMR) AF: 0.0612 AC: 2541 AN: 41516

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3326 AN: 25212

East Asian (EAS) AF: 0.0480 AC: 1797 AN: 37414

South Asian (SAS) AF: 0.0688 AC: 5517 AN: 80224

European-Finnish (FIN) AF: 0.0704 AC: 3603 AN: 51208

Middle Eastern (MID) AF: 0.159 AC: 847 AN: 5328

European-Non Finnish (NFE) AF: 0.106 AC: 112092 AN: 1053896

Other (OTH) AF: 0.109 AC: 6239 AN: 57316

GnomAD4 genome AF: 0.149 AC: 22584 AN: 151282 Hom.: 2174 Cov.: 31 AF XY: 0.144 AC XY: 10664 AN XY: 73926

African (AFR) AF: 0.276 AC: 11374 AN: 41146

American (AMR) AF: 0.0965 AC: 1468 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3466

East Asian (EAS) AF: 0.0390 AC: 201 AN: 5156

South Asian (SAS) AF: 0.0794 AC: 381 AN: 4798

European-Finnish (FIN) AF: 0.0582 AC: 604 AN: 10386

Middle Eastern (MID) AF: 0.193 AC: 56 AN: 290

European-Non Finnish (NFE) AF: 0.111 AC: 7544 AN: 67812

Other (OTH) AF: 0.151 AC: 317 AN: 2098

Alfa AF: 0.131 Hom.: 278

Bravo AF: 0.155

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.19
DANN	Benign	0.21
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs55657337; hg19: chr18-29101230; COSMIC: COSV99853069;