rs34065672

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001943.5(DSG2):​c.2708C>A​(p.Thr903Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T903I) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DSG2
NM_001943.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.848
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-AS1 (HGNC:51311): (DSG2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24525383).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DSG2NM_001943.5 linkuse as main transcriptc.2708C>A p.Thr903Asn missense_variant 15/15 ENST00000261590.13
DSG2-AS1NR_045216.1 linkuse as main transcriptn.1346-188G>T intron_variant, non_coding_transcript_variant
DSG2XM_047437315.1 linkuse as main transcriptc.2174C>A p.Thr725Asn missense_variant 16/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DSG2ENST00000261590.13 linkuse as main transcriptc.2708C>A p.Thr903Asn missense_variant 15/151 NM_001943.5 P1
DSG2-AS1ENST00000583706.5 linkuse as main transcriptn.1384-188G>T intron_variant, non_coding_transcript_variant 5
DSG2-AS1ENST00000657343.1 linkuse as main transcriptn.697-188G>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.27
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.49
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.13
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.039
D
Polyphen
0.45
P
Vest4
0.23
MutPred
0.18
Loss of sheet (P = 0.0357);
MVP
0.81
MPC
0.15
ClinPred
0.58
D
GERP RS
3.3
Varity_R
0.11
gMVP
0.26

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.

Other links and lift over

dbSNP: rs34065672; hg19: chr18-29126057; API