18-31101815-A-AC

Variant names:

• chr18-31101815-A-AC
• rs543480937
• NM_024422.6:c.69+87dupG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_024422.6(DSC2):​c.69+87dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 405,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0097 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: DSC2 NM_024422.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.29

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-31101815-A-AC is Benign according to our data. Variant chr18-31101815-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 1195346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0097 (330/34026) while in subpopulation AFR AF= 0.0319 (307/9620). AF 95% confidence interval is 0.029. There are 0 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSC2	NM_024422.6	c.69+87dupG		intron_variant	Intron 1 of 15	ENST00000280904.11	NP_077740.1
DSC2	NM_004949.5	c.69+87dupG		intron_variant	Intron 1 of 16		NP_004940.1
DSCAS	NR_110785.1	n.136+97dupC		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSC2	ENST00000280904.11	c.69+87_69+88insG		intron_variant	Intron 1 of 15	1	NM_024422.6	ENSP00000280904.6

Frequencies

GnomAD3 genomes AF: 0.00968 AC: 329 AN: 33986 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00520

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00197

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000629

Gnomad OTH AF: 0.0114

GnomAD4 exome AF: 0.000433 AC: 161 AN: 371766 Hom.: 0 Cov.: 17 AF XY: 0.000361 AC XY: 67 AN XY: 185816

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.000632

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000990

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000104

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00970 AC: 330 AN: 34026 Hom.: 0 Cov.: 31 AF XY: 0.00902 AC XY: 150 AN XY: 16632

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.00518

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00197

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000629

Gnomad4 OTH AF: 0.0112

Alfa AF: 0.00261 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 31, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs543480937; hg19: chr18-28681778;