18-31519887-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001943.5(DSG2):​c.166G>T​(p.Val56Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. V56M) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

DSG2
NM_001943.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37521866).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DSG2NM_001943.5 linkc.166G>T p.Val56Leu missense_variant Exon 3 of 15 ENST00000261590.13 NP_001934.2 Q14126
DSG2XM_047437315.1 linkc.-369G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 4 of 16 XP_047293271.1
DSG2XM_047437315.1 linkc.-369G>T 5_prime_UTR_variant Exon 4 of 16 XP_047293271.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DSG2ENST00000261590.13 linkc.166G>T p.Val56Leu missense_variant Exon 3 of 15 1 NM_001943.5 ENSP00000261590.8 Q14126

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.15
T;T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.015
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.77
T;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.87
L;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.17
Sift
Benign
0.031
D;.
Sift4G
Benign
0.16
T;T
Polyphen
0.13
B;.
Vest4
0.55
MutPred
0.58
Loss of MoRF binding (P = 0.0966);Loss of MoRF binding (P = 0.0966);
MVP
0.65
MPC
0.20
ClinPred
0.71
D
GERP RS
5.2
Varity_R
0.18
gMVP
0.76

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: rs121913013; hg19: chr18-29099850; API