rs10484326

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004415.4(DSP):c.274-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,613,050 control chromosomes in the GnomAD database, including 42,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3519 hom., cov: 33)

Exomes 𝑓: 0.23 ( 38759 hom. )

Consequence

DSP
NM_004415.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0860

Publications

17 publications found

Variant links:

Genes affected

DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DSP Gene-Disease associations (from GenCC):

keratosis palmoplantaris striata 2
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, G2P
arrhythmogenic cardiomyopathy with wooly hair and keratoderma
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen
arrhythmogenic right ventricular dysplasia 8
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
skin fragility-woolly hair-palmoplantar keratoderma syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Ambry Genetics, Orphanet
cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
dilated cardiomyopathy
Inheritance: AD Classification: STRONG Submitted by: ClinGen
lethal acantholytic epidermolysis bullosa
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
striate palmoplantar keratoderma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
severe dermatitis-multiple allergies-metabolic wasting syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

DSP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-7558085-T-C is Benign according to our data. Variant chr6-7558085-T-C is described in ClinVar as Benign. ClinVar VariationId is 137167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004415.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSP	NM_004415.4	MANE Select	c.274-31T>C	intron	N/A	NP_004406.2	P15924-1
DSP	NM_001319034.2		c.274-31T>C	intron	N/A	NP_001305963.1	P15924-3
DSP	NM_001008844.3		c.274-31T>C	intron	N/A	NP_001008844.1	P15924-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DSP	ENST00000379802.8	TSL:1 MANE Select	c.274-31T>C	intron	N/A	ENSP00000369129.3	P15924-1
DSP	ENST00000418664.3	TSL:1	c.274-31T>C	intron	N/A	ENSP00000396591.2	P15924-2
DSP	ENST00000713904.1		c.148-31T>C	intron	N/A	ENSP00000519203.1	A0AAQ5BH40

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31404

AN:

152106

Hom.:

3516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.0494

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.197

AC:

49393

AN:

251312

AF XY:

0.200

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.225

AC:

329155

AN:

1460826

Hom.:

38759

Cov.:

AF XY:

0.224

AC XY:

162683

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.165

AC:

5521

AN:

33444

American (AMR)

AF:

0.136

AC:

6104

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

7791

AN:

26132

East Asian (EAS)

AF:

0.0415

AC:

1649

AN:

39696

South Asian (SAS)

AF:

0.158

AC:

13585

AN:

86240

European-Finnish (FIN)

AF:

0.255

AC:

13633

AN:

53408

Middle Eastern (MID)

AF:

0.269

AC:

1550

AN:

5768

European-Non Finnish (NFE)

AF:

0.239

AC:

265543

AN:

1111070

Other (OTH)

AF:

0.228

AC:

13779

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12118

24236

36354

48472

60590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8938

17876

26814

35752

44690

<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:

0.206

AC:

31404

AN:

152224

Hom.:

3519

Cov.:

AF XY:

0.206

AC XY:

15305

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.167

AC:

6957

AN:

41550

American (AMR)

AF:

0.176

AC:

2689

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1063

AN:

3470

East Asian (EAS)

AF:

0.0490

AC:

254

AN:

5188

South Asian (SAS)

AF:

0.158

AC:

761

AN:

4826

European-Finnish (FIN)

AF:

0.267

AC:

2830

AN:

10588

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16148

AN:

67986

Other (OTH)

AF:

0.207

AC:

438

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1277

2554

3832

5109

6386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.226

Hom.:

7754

Bravo

AF:

0.199

Asia WGS

AF:

0.121

AC:

421

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.63

(source)

DANN

Benign

0.65

PhyloP100

0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

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