rs1426310

Positions:

chr18-31318331-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000257192.5(DSG1):c.31A>G(p.Met11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,610,274 control chromosomes in the GnomAD database, including 178,730 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15946 hom., cov: 32)

Exomes 𝑓: 0.46 ( 162784 hom. )

Consequence

DSG1
ENST00000257192.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

DSG1 (HGNC:3048): (desmoglein 1) This gene encodes a member of the desmoglein protein subfamily. Desmogleins, along with desmocollins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmoglein family members on chromosome 18. The encoded protein has been identified as a target of auto-antibodies in the autoimmune skin blistering disease pemphigus foliaceus. Disruption of this gene has also been associated with the skin diseases palmoplantar keratoderma and erythroderma. [provided by RefSeq, Feb 2015]

DSG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0042062E-4).

BP6

Variant 18-31318331-A-G is Benign according to our data. Variant chr18-31318331-A-G is described in ClinVar as [Benign]. Clinvar id is 402801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG1	NM_001942.4 linkuse as main transcript	c.31A>G	p.Met11Val	missense_variant	1/15	ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5 linkuse as main transcript	c.31A>G	p.Met11Val	missense_variant	1/15	1	NM_001942.4	ENSP00000257192	P1	Q02413-1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67773

AN:

151900

Hom.:

15949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.0585

Gnomad SAS

AF:

0.474

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.451

GnomAD3 exomes

AF:

0.422

AC:

105843

AN:

250724

Hom.:

25070

AF XY:

0.435

AC XY:

59016

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.0557

Gnomad SAS exome

AF:

0.486

Gnomad FIN exome

AF:

0.568

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.464

AC:

676571

AN:

1458256

Hom.:

162784

Cov.:

AF XY:

0.466

AC XY:

337985

AN XY:

725604

show subpopulations

Gnomad4 AFR exome

AF:

0.451

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.446

Gnomad4 EAS exome

AF:

0.0589

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.565

Gnomad4 NFE exome

AF:

0.483

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.446

AC:

67795

AN:

152018

Hom.:

15946

Cov.:

AF XY:

0.447

AC XY:

33241

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.441

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.456

Gnomad4 EAS

AF:

0.0584

Gnomad4 SAS

AF:

0.472

Gnomad4 FIN

AF:

0.562

Gnomad4 NFE

AF:

0.487

Gnomad4 OTH

AF:

0.449

Alfa

AF:

0.462

Hom.:

43525

Bravo

AF:

0.424

TwinsUK

AF:

0.497

AC:

1844

ALSPAC

AF:

0.477

AC:

1838

ESP6500AA

AF:

0.466

AC:

2051

ESP6500EA

AF:

0.487

AC:

4191

ExAC

AF:

0.434

AC:

52735

Asia WGS

AF:

0.295

AC:

1026

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 27, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Palmoplantar keratoderma i, striate, focal, or diffuse

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Severe dermatitis-multiple allergies-metabolic wasting syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.038

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.013

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.13

MetaRNN

Benign

0.00020

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.47

REVEL

Benign

0.071

Sift

Benign

0.96

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.015

MPC

0.073

ClinPred

0.0039

GERP RS

4.3

Varity_R

0.054

gMVP

0.18

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