rs786205428

Positions:

• chr18-31068321-CAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000280904.11(DSC2):​c.2509-111_2509-110del variant causes a intron change. The variant allele was found at a frequency of 0.0000411 in 1,461,232 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: DSC2 ENST00000280904.11 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74

Genes affected

DSC2 (HGNC:3036): (desmocollin 2) This gene encodes a member of the desmocollin protein subfamily. Desmocollins, along with desmogleins, 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 desmocollin family members on chromosome 18. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia-11, and reduced protein expression has been described in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC2	NM_024422.6	c.2509-111_2509-110del		intron_variant		ENST00000280904.11	NP_077740.1
DSC2	NM_001406507.1	c.2101_2102del	p.Leu701AspfsTer2	frameshift_variant	16/17		NP_001393436.1
DSC2	NM_004949.5	c.2530_2531del	p.Leu844AspfsTer2	frameshift_variant	16/17		NP_004940.1
DSC2	NM_001406506.1	c.2080-111_2080-110del		intron_variant			NP_001393435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSC2	ENST00000251081.8	c.2530_2531del	p.Leu844AspfsTer2	frameshift_variant	16/17	1		ENSP00000251081
DSC2	ENST00000280904.11	c.2509-111_2509-110del		intron_variant		1	NM_024422.6	ENSP00000280904	P1
DSC2	ENST00000648081.1	c.2080-111_2080-110del		intron_variant				ENSP00000497441
DSC2	ENST00000682357.1	c.2080-111_2080-110del		intron_variant				ENSP00000507826

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000411 AC: 60 AN: 1461232 Hom.: 0 AF XY: 0.0000440 AC XY: 32 AN XY: 726964

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs786205428; hg19: chr18-28648287;