rs2199301

Positions:

• chr18-31330652-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001942.4(DSG1):​c.517+616A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,988 control chromosomes in the GnomAD database, including 14,278 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14278 hom., cov: 32)
• Consequence: DSG1 NM_001942.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG1	NM_001942.4	c.517+616A>G		intron_variant		ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5	c.517+616A>G		intron_variant		1	NM_001942.4	ENSP00000257192.4

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62962 AN: 151870 Hom.: 14283 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.414 AC: 62974 AN: 151988 Hom.: 14278 Cov.: 32 AF XY: 0.417 AC XY: 30994 AN XY: 74290

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.0584

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.432

Alfa AF: 0.471 Hom.: 22391

Bravo AF: 0.384

Asia WGS AF: 0.288 AC: 999 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs2199301; hg19: chr18-28910615;