rs2076303

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004415.4(DSP):c.1904-49T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,583,700 control chromosomes in the GnomAD database, including 150,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14099 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136094 hom. )

Consequence

DSP
NM_004415.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.222

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-7571793-T-A is Benign according to our data. Variant chr6-7571793-T-A is described in ClinVar as [Benign]. Clinvar id is 259382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7571793-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4 link	c.1904-49T>A	intron_variant	Intron 14 of 23	ENST00000379802.8	NP_004406.2	P15924-1B4DKX6
DSP	NM_001319034.2 link	c.1904-49T>A	intron_variant	Intron 14 of 23		NP_001305963.1	P15924-3B4DKX6
DSP	NM_001008844.3 link	c.1904-49T>A	intron_variant	Intron 14 of 23		NP_001008844.1	P15924-2B4DKX6Q4LE79

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DSP	ENST00000379802.8 link	c.1904-49T>A	intron_variant	Intron 14 of 23	1	NM_004415.4	ENSP00000369129.3	P15924-1
DSP	ENST00000418664.2 link	c.1904-49T>A	intron_variant	Intron 14 of 23	1		ENSP00000396591.2	P15924-2
DSP	ENST00000710359.1 link	c.1904-49T>A	intron_variant	Intron 14 of 23			ENSP00000518230.1
DSP	ENST00000684395.1 link	n.496T>A	non_coding_transcript_exon_variant	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63797

AN:

151920

Hom.:

14095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.422

GnomAD3 exomes

AF:

0.462

AC:

112461

AN:

243280

Hom.:

27770

AF XY:

0.458

AC XY:

60539

AN XY:

132304

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.373

Gnomad EAS exome

AF:

0.763

Gnomad SAS exome

AF:

0.490

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.412

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.428

AC:

613045

AN:

1431662

Hom.:

136094

Cov.:

AF XY:

0.430

AC XY:

306946

AN XY:

714076

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.569

Gnomad4 ASJ exome

AF:

0.371

Gnomad4 EAS exome

AF:

0.797

Gnomad4 SAS exome

AF:

0.486

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.412

Gnomad4 OTH exome

AF:

0.432

GnomAD4 genome

AF:

0.420

AC:

63829

AN:

152038

Hom.:

14099

Cov.:

AF XY:

0.425

AC XY:

31550

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.376

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.767

Gnomad4 SAS

AF:

0.500

Gnomad4 FIN

AF:

0.315

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.422

Alfa

AF:

0.403

Hom.:

2328

Bravo

AF:

0.436

Asia WGS

AF:

0.550

AC:

1910

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lethal acantholytic epidermolysis bullosa

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Woolly hair-skin fragility syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Keratosis palmoplantaris striata 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.3

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over