rs200691513

Positions:

chr18-31545954-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001943.5(DSG2):c.2568A>C(p.Lys856Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DSG2
NM_001943.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.775

Variant links:

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 links:

DSG2-AS1 (HGNC:51311): (DSG2 antisense RNA 1)

DSG2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040987134).

BP6

Variant 18-31545954-A-C is Benign according to our data. Variant chr18-31545954-A-C is described in ClinVar as [Benign]. Clinvar id is 192185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DSG2	NM_001943.5 linkuse as main transcript	c.2568A>C	p.Lys856Asn	missense_variant	15/15	ENST00000261590.13
DSG2-AS1	NR_045216.1 linkuse as main transcript	n.1346-48T>G		intron_variant, non_coding_transcript_variant
DSG2	XM_047437315.1 linkuse as main transcript	c.2034A>C	p.Lys678Asn	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DSG2	ENST00000261590.13 linkuse as main transcript	c.2568A>C	p.Lys856Asn	missense_variant	15/15	1	NM_001943.5	P1
DSG2-AS1	ENST00000583706.5 linkuse as main transcript	n.1384-48T>G		intron_variant, non_coding_transcript_variant		5
DSG2-AS1	ENST00000657343.1 linkuse as main transcript	n.697-48T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151966

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000479

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00279

AC:

4071

AN:

1457766

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

2097

AN XY:

725122

show subpopulations

Gnomad4 AFR exome

AF:

0.00517

Gnomad4 AMR exome

AF:

0.0269

Gnomad4 ASJ exome

AF:

0.00169

Gnomad4 EAS exome

AF:

0.0141

Gnomad4 SAS exome

AF:

0.000685

Gnomad4 FIN exome

AF:

0.0188

Gnomad4 NFE exome

AF:

0.000832

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000921

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000474

ExAC

AF:

0.0327

AC:

3951

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Aug 18, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

REVEL

Benign

0.093

Sift

Benign

0.38

Sift4G

Benign

0.37

Polyphen

0.87

Vest4

0.059

MutPred

0.26

Loss of methylation at K856 (P = 6e-04);

MPC

0.40

ClinPred

0.0092

GERP RS

0.67

Varity_R

0.025

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over