rs5823783

Variant names:

• chr18-31086560-TTAA-T
• rs5823783
• NM_024422.6:c.942+13_942+15delTTA

Your query was ambiguous. Multiple possible variants found:

• chr18-31086560-TTAA-T
• chr18-31086560-TTAA-TTAATAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024422.6(DSC2):​c.942+13_942+15delTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,614,070 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: DSC2 NM_024422.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 1 publications found

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]

DSC2 Gene-Disease associations (from GenCC):

• familial isolated arrhythmogenic right ventricular dysplasia

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• arrhythmogenic right ventricular dysplasia 11

  Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00233 (355/152338) while in subpopulation AFR AF = 0.0082 (341/41584). AF 95% confidence interval is 0.00748. There are 2 homozygotes in GnomAd4. There are 161 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSC2	NM_024422.6	c.942+13_942+15delTTA		intron_variant	Intron 7 of 15	ENST00000280904.11	NP_077740.1
DSC2	NM_004949.5	c.942+13_942+15delTTA		intron_variant	Intron 7 of 16		NP_004940.1
DSC2	NM_001406506.1	c.513+13_513+15delTTA		intron_variant	Intron 7 of 15		NP_001393435.1
DSC2	NM_001406507.1	c.513+13_513+15delTTA		intron_variant	Intron 7 of 16		NP_001393436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSC2	ENST00000280904.11	c.942+13_942+15delTTA		intron_variant	Intron 7 of 15	1	NM_024422.6	ENSP00000280904.6

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 354 AN: 152220 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00818

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.000242 AC: 354 AN: 1461732 Hom.: 1 AF XY: 0.000224 AC XY: 163 AN XY: 727172

African (AFR) AF: 0.00917 AC: 307 AN: 33464

American (AMR) AF: 0.000224 AC: 10 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111892

Other (OTH) AF: 0.000480 AC: 29 AN: 60392

GnomAD4 genome AF: 0.00233 AC: 355 AN: 152338 Hom.: 2 Cov.: 32 AF XY: 0.00216 AC XY: 161 AN XY: 74494

African (AFR) AF: 0.00820 AC: 341 AN: 41584

American (AMR) AF: 0.000327 AC: 5 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.000854 Hom.: 9958

Bravo AF: 0.00264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5823783; hg19: chr18-28666526;