18-31101800-C-G

Variant names:

• chr18-31101800-C-G
• rs545884156
• NM_024422.6:c.69+103G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024422.6(DSC2):​c.69+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,252,718 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (8 hom., cov: 30)
  • Exomes 𝑓: 0.00087 (12 hom.)
• Consequence: DSC2 NM_024422.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.791
• Publications: 0 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]

DSCAS (HGNC:51116): (DSC1/DSC2 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 18-31101800-C-G is Benign according to our data. Variant chr18-31101800-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1212510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00468 (712/152120) while in subpopulation AFR AF = 0.0144 (599/41498). AF 95% confidence interval is 0.0135. There are 8 homozygotes in GnomAd4. There are 322 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR,SD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSC2	NM_024422.6	MANE Select	c.69+103G>C		intron	N/A	NP_077740.1	Q02487-1
	DSC2	NM_004949.5		c.69+103G>C		intron	N/A	NP_004940.1	Q02487-2
	DSCAS	NR_110785.1		n.136+77C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSC2	ENST00000280904.11	TSL:1 MANE Select	c.69+103G>C		intron	N/A	ENSP00000280904.6	Q02487-1
	DSC2	ENST00000251081.8	TSL:1	c.69+103G>C		intron	N/A	ENSP00000251081.6	Q02487-2
	DSC2	ENST00000713707.1		c.69+103G>C		intron	N/A	ENSP00000519010.1	A0AAQ5BGP6

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 711 AN: 152014 Hom.: 8 Cov.: 30

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000866 AC: 953 AN: 1100598 Hom.: 12 Cov.: 14 AF XY: 0.000858 AC XY: 471 AN XY: 548792

African (AFR) AF: 0.0123 AC: 275 AN: 22364

American (AMR) AF: 0.000774 AC: 22 AN: 28426

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 277 AN: 20394

East Asian (EAS) AF: 0.00 AC: 0 AN: 27990

South Asian (SAS) AF: 0.000261 AC: 18 AN: 69076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30312

Middle Eastern (MID) AF: 0.00601 AC: 25 AN: 4162

European-Non Finnish (NFE) AF: 0.000267 AC: 227 AN: 851436

Other (OTH) AF: 0.00235 AC: 109 AN: 46438

GnomAD4 genome AF: 0.00468 AC: 712 AN: 152120 Hom.: 8 Cov.: 30 AF XY: 0.00433 AC XY: 322 AN XY: 74356

African (AFR) AF: 0.0144 AC: 599 AN: 41498

American (AMR) AF: 0.00170 AC: 26 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 67962

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.00513

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.72
PhyloP100		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs545884156; hg19: chr18-28681763;