chr18-31476502-A-G

Variant names:

• chr18-31476502-A-G
• rs1466379
• NM_001944.3:c.*242A>G

Variant summary

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

The NM_001944.3(DSG3):​c.*242A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 395,736 control chromosomes in the GnomAD database, including 8,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5048 hom., cov: 32)
  • Exomes 𝑓: 0.16 (3697 hom.)
• Consequence: DSG3 NM_001944.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0720
• Publications: 7 publications found

Genes affected

DSG3 (HGNC:3050): (desmoglein 3) 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. The encoded protein has been identified as the autoantigen of the autoimmune blistering disease pemphigus vulgaris. [provided by RefSeq, Jan 2016]

DSG3 Gene-Disease associations (from GenCC):

• blistering, acantholytic, of oral and laryngeal mucosa

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 18-31476502-A-G is Benign according to our data. Variant chr18-31476502-A-G is described in ClinVar as Benign. ClinVar VariationId is 1180073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG3	NM_001944.3	c.*242A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000257189.5	NP_001935.2
DSG3	XM_011525850.3	c.*242A>G		3_prime_UTR_variant	Exon 16 of 16		XP_011524152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG3	ENST00000257189.5	c.*242A>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_001944.3	ENSP00000257189.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33827 AN: 152008 Hom.: 5021 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.162 AC: 39445 AN: 243610 Hom.: 3697 Cov.: 4 AF XY: 0.160 AC XY: 19818 AN XY: 123704

African (AFR) AF: 0.436 AC: 3105 AN: 7114

American (AMR) AF: 0.125 AC: 1118 AN: 8910

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 1071 AN: 8472

East Asian (EAS) AF: 0.174 AC: 3492 AN: 20054

South Asian (SAS) AF: 0.236 AC: 1523 AN: 6452

European-Finnish (FIN) AF: 0.172 AC: 2817 AN: 16340

Middle Eastern (MID) AF: 0.150 AC: 179 AN: 1192

European-Non Finnish (NFE) AF: 0.147 AC: 23444 AN: 159554

Other (OTH) AF: 0.174 AC: 2696 AN: 15522

GnomAD4 genome AF: 0.223 AC: 33907 AN: 152126 Hom.: 5048 Cov.: 32 AF XY: 0.220 AC XY: 16368 AN XY: 74348

African (AFR) AF: 0.426 AC: 17670 AN: 41444

American (AMR) AF: 0.146 AC: 2232 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3472

East Asian (EAS) AF: 0.132 AC: 681 AN: 5174

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10600

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9690 AN: 67998

Other (OTH) AF: 0.193 AC: 408 AN: 2114

Alfa AF: 0.165 Hom.: 5127

Bravo AF: 0.228

Asia WGS AF: 0.210 AC: 733 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		-0.072
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: rs1466379; hg19: chr18-29056465;