18-31058866-G-A

Variant names:

• chr18-31058866-G-A
• rs1790695
• NM_024422.6:c.*9149C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024422.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSC2	NM_024422.6	MANE Select	c.*9149C>T		3_prime_UTR	Exon 16 of 16	NP_077740.1
	DSC2	NM_004949.5		c.*9357C>T		3_prime_UTR	Exon 17 of 17	NP_004940.1
	DSC2	NM_001406506.1		c.*9149C>T		3_prime_UTR	Exon 16 of 16	NP_001393435.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSC2	ENST00000280904.11	TSL:1 MANE Select	c.*9149C>T		3_prime_UTR	Exon 16 of 16	ENSP00000280904.6
	DSC2	ENST00000251081.8	TSL:1	c.*9357C>T		3_prime_UTR	Exon 17 of 17	ENSP00000251081.6
	DSC2	ENST00000713685.1		c.*9149C>T		3_prime_UTR	Exon 16 of 16	ENSP00000518988.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.665 AC: 27542 AN: 41432

American (AMR) AF: 0.681 AC: 10392 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2481 AN: 3468

East Asian (EAS) AF: 0.703 AC: 3630 AN: 5164

South Asian (SAS) AF: 0.532 AC: 2560 AN: 4808

European-Finnish (FIN) AF: 0.529 AC: 5557 AN: 10506

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45268 AN: 67956

Other (OTH) AF: 0.676 AC: 1425 AN: 2108

Alfa AF: 0.644 Hom.: 11759

Bravo AF: 0.674

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.71
DANN	Benign	0.55
PhyloP100		-0.28

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

Other links and lift over

dbSNP: rs1790695; hg19: chr18-28638832;