18-30994547-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001941.5(DSC3):c.2494-176del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,422,866 control chromosomes in the GnomAD database, including 1,468 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (148 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1320 hom.)
• Consequence: DSC3 NM_001941.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.499

Genes affected

DSC3 (HGNC:3037): (desmocollin 3) The protein encoded by this gene is a calcium-dependent glycoprotein that is a member of the desmocollin subfamily of the cadherin superfamily. These desmosomal family members, along with the desmogleins, are found primarily in epithelial cells where they constitute the adhesive proteins of the desmosome cell-cell junction and are required for cell adhesion and desmosome formation. The desmosomal family members are arranged in two clusters on chromosome 18, occupying less than 650 kb combined. Mutations in this gene are a cause of hypotrichosis and recurrent skin vesicles disorder. The protein can act as an autoantigen in pemphigus diseases, and it is also considered to be a biomarker for some cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 18-30994547-AG-A is Benign according to our data. Variant chr18-30994547-AG-A is described in ClinVar as [Benign]. Clinvar id is 1287128.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSC3	NM_001941.5	c.2494-176del		intron_variant		ENST00000360428.9
DSC3	NM_024423.4	c.2494-52del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSC3	ENST00000360428.9	c.2494-176del		intron_variant		1	NM_001941.5	P1
DSC3	ENST00000434452.5	c.2494-52del		intron_variant		5
DSC3	ENST00000584980.1	c.618-52del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5290 AN: 152204 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0374 AC: 9283 AN: 247992 Hom.: 260 AF XY: 0.0399 AC XY: 5341 AN XY: 133946

Gnomad AFR exome AF: 0.0173

Gnomad AMR exome AF: 0.0198

Gnomad ASJ exome AF: 0.0284

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.0535

Gnomad FIN exome AF: 0.0632

Gnomad NFE exome AF: 0.0431

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0414 AC: 52638 AN: 1270544 Hom.: 1320 Cov.: 16 AF XY: 0.0422 AC XY: 27015 AN XY: 640192

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.0200

Gnomad4 ASJ exome AF: 0.0262

Gnomad4 EAS exome AF: 0.000142

Gnomad4 SAS exome AF: 0.0551

Gnomad4 FIN exome AF: 0.0626

Gnomad4 NFE exome AF: 0.0428

Gnomad4 OTH exome AF: 0.0406

GnomAD4 genome AF: 0.0347 AC: 5288 AN: 152322 Hom.: 148 Cov.: 32 AF XY: 0.0364 AC XY: 2713 AN XY: 74488

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0501

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.0454

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0312 Hom.: 31

Bravo AF: 0.0295

Asia WGS AF: 0.0170 AC: 60 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs5823774; hg19: chr18-28574513;