rs5823783

Positions:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024422.6(DSC2):​c.942+13_942+15del 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

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 Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSC2	NM_024422.6	c.942+13_942+15del		intron_variant		ENST00000280904.11
DSC2	NM_001406506.1	c.513+13_513+15del		intron_variant
DSC2	NM_001406507.1	c.513+13_513+15del		intron_variant
DSC2	NM_004949.5	c.942+13_942+15del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSC2	ENST00000280904.11	c.942+13_942+15del		intron_variant		1	NM_024422.6	P1
DSC2	ENST00000251081.8	c.942+13_942+15del		intron_variant		1
DSC2	ENST00000648081.1	c.513+13_513+15del		intron_variant
DSC2	ENST00000682357.1	c.513+13_513+15del		intron_variant

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

Gnomad4 AFR exome AF: 0.00917

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.000480

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

Gnomad4 AFR AF: 0.00820

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000854 Hom.: 9958

Bravo AF: 0.00264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5823783; hg19: chr18-28666526;