18-31456879-C-G

Variant names:

• chr18-31456879-C-G
• rs66889852
• NM_001944.3:c.85-114C>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.85-114C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,017,686 control chromosomes in the GnomAD database, including 936 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (491 hom., cov: 32)
  • Exomes 𝑓: 0.021 (445 hom.)
• Consequence: DSG3 NM_001944.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.765
• Publications: 0 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=-0.9).
• BP6: Variant 18-31456879-C-G is Benign according to our data. Variant chr18-31456879-C-G is described in ClinVar as Benign. ClinVar VariationId is 1284172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG3	NM_001944.3	MANE Select	c.85-114C>G		intron	N/A	NP_001935.2	P32926

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG3	ENST00000257189.5	TSL:1 MANE Select	c.85-114C>G		intron	N/A	ENSP00000257189.4	P32926
	DSG3	ENST00000851332.1		c.49-4348C>G		intron	N/A	ENSP00000521391.1

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8503 AN: 152100 Hom.: 490 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0430

GnomAD4 exome AF: 0.0206 AC: 17802 AN: 865468 Hom.: 445 AF XY: 0.0197 AC XY: 8646 AN XY: 438862

African (AFR) AF: 0.159 AC: 3133 AN: 19730

American (AMR) AF: 0.0173 AC: 411 AN: 23748

Ashkenazi Jewish (ASJ) AF: 0.00392 AC: 64 AN: 16322

East Asian (EAS) AF: 0.00 AC: 0 AN: 34672

South Asian (SAS) AF: 0.00511 AC: 245 AN: 47908

European-Finnish (FIN) AF: 0.0426 AC: 1972 AN: 46240

Middle Eastern (MID) AF: 0.0448 AC: 132 AN: 2944

European-Non Finnish (NFE) AF: 0.0171 AC: 10884 AN: 634896

Other (OTH) AF: 0.0246 AC: 961 AN: 39008

GnomAD4 genome AF: 0.0560 AC: 8521 AN: 152218 Hom.: 491 Cov.: 32 AF XY: 0.0547 AC XY: 4069 AN XY: 74444

African (AFR) AF: 0.154 AC: 6387 AN: 41538

American (AMR) AF: 0.0226 AC: 345 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4824

European-Finnish (FIN) AF: 0.0433 AC: 459 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1181 AN: 67990

Other (OTH) AF: 0.0426 AC: 90 AN: 2114

Alfa AF: 0.0400 Hom.: 33

Bravo AF: 0.0582

Asia WGS AF: 0.00982 AC: 36 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.50
PhyloP100		-0.77
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: rs66889852; hg19: chr18-29036842;