6-7567737-C-T

Variant names:

Variant summary

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

The NM_004415.4(DSP):c.1141-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 1,611,848 control chromosomes in the GnomAD database, including 471,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 45824 hom., cov: 31)

Exomes 𝑓: 0.76 ( 425533 hom. )

Consequence

DSP
NM_004415.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0290

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=-0.85).

BP6

Variant 6-7567737-C-T is Benign according to our data. Variant chr6-7567737-C-T is described in ClinVar as [Benign]. Clinvar id is 259381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7567737-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4 link	c.1141-44C>T	intron_variant	Intron 9 of 23	ENST00000379802.8	NP_004406.2	P15924-1B4DKX6
DSP	NM_001319034.2 link	c.1141-44C>T	intron_variant	Intron 9 of 23		NP_001305963.1	P15924-3B4DKX6
DSP	NM_001008844.3 link	c.1141-44C>T	intron_variant	Intron 9 of 23		NP_001008844.1	P15924-2B4DKX6Q4LE79
DSP	NM_001406591.1 link	c.1141-44C>T	intron_variant	Intron 9 of 10		NP_001393520.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DSP	ENST00000379802.8 link	c.1141-44C>T	intron_variant	Intron 9 of 23	1	NM_004415.4	ENSP00000369129.3	P15924-1
DSP	ENST00000418664.2 link	c.1141-44C>T	intron_variant	Intron 9 of 23	1		ENSP00000396591.2	P15924-2
DSP	ENST00000710359.1 link	c.1141-44C>T	intron_variant	Intron 9 of 23			ENSP00000518230.1
DSP	ENST00000682228.1 link	n.752C>T	non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.775

AC:

117801

AN:

151956

Hom.:

45804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.797

Gnomad AMI

AF:

0.784

Gnomad AMR

AF:

0.781

Gnomad ASJ

AF:

0.843

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.686

Gnomad FIN

AF:

0.717

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.769

Gnomad OTH

AF:

0.779

GnomAD3 exomes

AF:

0.760

AC:

190311

AN:

250490

Hom.:

72656

AF XY:

0.756

AC XY:

102337

AN XY:

135424

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.767

Gnomad ASJ exome

AF:

0.835

Gnomad EAS exome

AF:

0.805

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.714

Gnomad NFE exome

AF:

0.767

Gnomad OTH exome

AF:

0.769

GnomAD4 exome

AF:

0.763

AC:

1113092

AN:

1459774

Hom.:

425533

Cov.:

AF XY:

0.761

AC XY:

552552

AN XY:

726266

show subpopulations

Gnomad4 AFR exome

AF:

0.797

Gnomad4 AMR exome

AF:

0.772

Gnomad4 ASJ exome

AF:

0.834

Gnomad4 EAS exome

AF:

0.834

Gnomad4 SAS exome

AF:

0.684

Gnomad4 FIN exome

AF:

0.713

Gnomad4 NFE exome

AF:

0.765

Gnomad4 OTH exome

AF:

0.773

GnomAD4 genome

AF:

0.775

AC:

117866

AN:

152074

Hom.:

45824

Cov.:

AF XY:

0.773

AC XY:

57405

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.797

Gnomad4 AMR

AF:

0.781

Gnomad4 ASJ

AF:

0.843

Gnomad4 EAS

AF:

0.812

Gnomad4 SAS

AF:

0.686

Gnomad4 FIN

AF:

0.717

Gnomad4 NFE

AF:

0.769

Gnomad4 OTH

AF:

0.775

Alfa

AF:

0.769

Hom.:

9595

Bravo

AF:

0.786

Asia WGS

AF:

0.699

AC:

2431

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 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

-0.85

CADD

Benign

1.9

DANN

Benign

0.43

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