rs2842691

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.3084+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,547,294 control chromosomes in the GnomAD database, including 481,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45585 hom., cov: 31)

Exomes 𝑓: 0.79 ( 435431 hom. )

Consequence

DSP
NM_004415.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.572

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=-0.89).

BP6

Variant 6-7578590-G-A is Benign according to our data. Variant chr6-7578590-G-A is described in ClinVar as [Benign]. Clinvar id is 259384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7578590-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4 link	c.3084+28G>A	intron_variant	Intron 22 of 23	ENST00000379802.8	NP_004406.2	P15924-1B4DKX6
DSP	NM_001319034.2 link	c.3084+28G>A	intron_variant	Intron 22 of 23		NP_001305963.1	P15924-3B4DKX6
DSP	NM_001008844.3 link	c.3084+28G>A	intron_variant	Intron 22 of 23		NP_001008844.1	P15924-2B4DKX6Q4LE79

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DSP	ENST00000379802.8 link	c.3084+28G>A	intron_variant	Intron 22 of 23	1	NM_004415.4	ENSP00000369129.3	P15924-1
DSP	ENST00000418664.2 link	c.3084+28G>A	intron_variant	Intron 22 of 23	1		ENSP00000396591.2	P15924-2
DSP	ENST00000710359.1 link	c.3084+28G>A	intron_variant	Intron 22 of 23			ENSP00000518230.1

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117198

AN:

151430

Hom.:

45551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.730

Gnomad AMI

AF:

0.864

Gnomad AMR

AF:

0.805

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.798

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.834

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.798

GnomAD3 exomes

AF:

0.781

AC:

194938

AN:

249528

Hom.:

76273

AF XY:

0.782

AC XY:

105435

AN XY:

134870

show subpopulations

Gnomad AFR exome

AF:

0.730

Gnomad AMR exome

AF:

0.789

Gnomad ASJ exome

AF:

0.820

Gnomad EAS exome

AF:

0.803

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.718

Gnomad NFE exome

AF:

0.801

Gnomad OTH exome

AF:

0.789

GnomAD4 exome

AF:

0.789

AC:

1101582

AN:

1395748

Hom.:

435431

Cov.:

AF XY:

0.789

AC XY:

551001

AN XY:

698324

show subpopulations

Gnomad4 AFR exome

AF:

0.728

Gnomad4 AMR exome

AF:

0.795

Gnomad4 ASJ exome

AF:

0.818

Gnomad4 EAS exome

AF:

0.812

Gnomad4 SAS exome

AF:

0.747

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.796

Gnomad4 OTH exome

AF:

0.791

GnomAD4 genome

AF:

0.774

AC:

117286

AN:

151546

Hom.:

45585

Cov.:

AF XY:

0.772

AC XY:

57155

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.730

Gnomad4 AMR

AF:

0.805

Gnomad4 ASJ

AF:

0.827

Gnomad4 EAS

AF:

0.798

Gnomad4 SAS

AF:

0.749

Gnomad4 FIN

AF:

0.715

Gnomad4 NFE

AF:

0.798

Gnomad4 OTH

AF:

0.794

Alfa

AF:

0.782

Hom.:

8339

Bravo

AF:

0.781

Asia WGS

AF:

0.730

AC:

2532

AN:

3470

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 13, 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

-0.89

CADD

Benign

1.4

DANN

Benign

0.34

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