rs1790695

Positions:

• chr18-31058866-G-A
• chr18-31058866-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024422.6(DSC2):​c.*9149C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,918 control chromosomes in the GnomAD database, including 32,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (32798 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: DSC2 NM_024422.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC2	NM_024422.6	c.*9149C>T		3_prime_UTR_variant	16/16	ENST00000280904.11	NP_077740.1
DSC2	NM_004949.5	c.*9357C>T		3_prime_UTR_variant	17/17		NP_004940.1
DSC2	NM_001406506.1	c.*9149C>T		3_prime_UTR_variant	16/16		NP_001393435.1
DSC2	NM_001406507.1	c.*9357C>T		3_prime_UTR_variant	17/17		NP_001393436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSC2	ENST00000280904	c.*9149C>T		3_prime_UTR_variant	16/16	1	NM_024422.6	ENSP00000280904.6
DSC2	ENST00000251081	c.*9357C>T		3_prime_UTR_variant	17/17	1		ENSP00000251081.6

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99560 AN: 151788 Hom.: 32754 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.500 AC: 6 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.656 AC: 99661 AN: 151906 Hom.: 32798 Cov.: 32 AF XY: 0.648 AC XY: 48128 AN XY: 74216

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.676

Alfa AF: 0.621 Hom.: 5171

Bravo AF: 0.674

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.55

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: rs1790695; hg19: chr18-28638832;