18-31101800-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSC2	NM_024422.6	c.69+103G>C		intron_variant	Intron 1 of 15	ENST00000280904.11	NP_077740.1
DSC2	NM_004949.5	c.69+103G>C		intron_variant	Intron 1 of 16		NP_004940.1
DSCAS	NR_110785.1	n.136+77C>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSC2	ENST00000280904.11	c.69+103G>C		intron_variant	Intron 1 of 15	1	NM_024422.6	ENSP00000280904.6

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

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.000774

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000261

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000267

Gnomad4 OTH exome AF: 0.00235

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

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.00513

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 11, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs545884156; hg19: chr18-28681763;