chr18-31068098-G-T

Position:

• chr18-31068098-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000280904.11(DSC2):​c.2623C>A​(p.Arg875=) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R875R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DSC2 ENST00000280904.11 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSC2	NM_024422.6	c.2623C>A	p.Arg875=	synonymous_variant	16/16	ENST00000280904.11	NP_077740.1
DSC2	NM_001406506.1	c.2194C>A	p.Arg732=	synonymous_variant	16/16		NP_001393435.1
DSC2	NM_001406507.1	c.*125C>A		3_prime_UTR_variant	17/17		NP_001393436.1
DSC2	NM_004949.5	c.*125C>A		3_prime_UTR_variant	17/17		NP_004940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSC2	ENST00000280904.11	c.2623C>A	p.Arg875=	synonymous_variant	16/16	1	NM_024422.6	ENSP00000280904	P1
DSC2	ENST00000251081.8	c.*125C>A		3_prime_UTR_variant	17/17	1		ENSP00000251081
DSC2	ENST00000648081.1	c.2194C>A	p.Arg732=	synonymous_variant	17/17			ENSP00000497441
DSC2	ENST00000682357.1	c.2194C>A	p.Arg732=	synonymous_variant	16/16			ENSP00000507826

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.72

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: rs727504823; hg19: chr18-28648064;