18-31328127-G-A

Position:

• chr18-31328127-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001942.4(DSG1):​c.217-62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,566,658 control chromosomes in the GnomAD database, including 206,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17716 hom., cov: 32)
  • Exomes 𝑓: 0.51 (188946 hom.)
• Consequence: DSG1 NM_001942.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.342

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-31328127-G-A is Benign according to our data. Variant chr18-31328127-G-A is described in ClinVar as [Benign]. Clinvar id is 1236050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG1	NM_001942.4	c.217-62G>A		intron_variant		ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5	c.217-62G>A		intron_variant		1	NM_001942.4	ENSP00000257192.4

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71339 AN: 151790 Hom.: 17721 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.0976

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.508 AC: 719024 AN: 1414750 Hom.: 188946 AF XY: 0.513 AC XY: 361233 AN XY: 703912

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.468

Gnomad4 EAS exome AF: 0.0967

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.470 AC: 71353 AN: 151908 Hom.: 17716 Cov.: 32 AF XY: 0.474 AC XY: 35207 AN XY: 74238

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.0978

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.486

Alfa AF: 0.477 Hom.: 3209

Bravo AF: 0.442

Asia WGS AF: 0.372 AC: 1293 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.78
DANN	Benign	0.68

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: rs2303465; hg19: chr18-28908090;