Genetic Variant DSC2:c.69+87dupG (chr18-31101815-A-AC) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS1

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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.29

Publications

0 publications found

Variant links:

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 links:

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

DSCAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSC2	NM_024422.6	MANE Select	c.69+87dupG	intron	N/A	NP_077740.1	Q02487-1
DSC2	NM_004949.5		c.69+87dupG	intron	N/A	NP_004940.1	Q02487-2
DSCAS	NR_110785.1		n.136+97dupC	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSC2	ENST00000280904.11	TSL:1 MANE Select	c.69+87_69+88insG	intron	N/A	ENSP00000280904.6	Q02487-1
DSC2	ENST00000251081.8	TSL:1	c.69+87_69+88insG	intron	N/A	ENSP00000251081.6	Q02487-2
DSC2	ENST00000713707.1		c.69+87_69+88insG	intron	N/A	ENSP00000519010.1	A0AAQ5BGP6

Frequencies

GnomAD3 genomes

AF:

0.00968

AC:

329

AN:

33986

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.000361

AC XY:

AN XY:

185816

show subpopulations

African (AFR)

AF:

0.0148

AC:

131

AN:

8868

American (AMR)

AF:

0.000632

AC:

AN:

11074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9164

East Asian (EAS)

AF:

0.00

AC:

AN:

8186

South Asian (SAS)

AF:

0.0000990

AC:

AN:

20202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8248

Middle Eastern (MID)

AF:

0.000889

AC:

AN:

2250

European-Non Finnish (NFE)

AF:

0.0000104

AC:

AN:

288682

Other (OTH)

AF:

0.00106

AC:

AN:

15092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00970

AC:

330

AN:

34026

Hom.:

Cov.:

AF XY:

0.00902

AC XY:

150

AN XY:

16632

show subpopulations

African (AFR)

AF:

0.0319

AC:

307

AN:

9620

American (AMR)

AF:

0.00518

AC:

AN:

2894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

970

East Asian (EAS)

AF:

0.00

AC:

AN:

1478

South Asian (SAS)

AF:

0.00197

AC:

AN:

1014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000629

AC:

AN:

15904

Other (OTH)

AF:

0.0112

AC:

AN:

448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00261

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over