Variant chr6-7575273-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1

The NM_004415.4(DSP):c.2437-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 817,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00092 ( 3 hom., cov: 33)

Exomes 𝑓: 0.026 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DSP
NM_004415.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.0620

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 -12 ACMG points.

BP6

Variant 6-7575273-CT-C is Benign according to our data. Variant chr6-7575273-CT-C is described in ClinVar as [Benign]. Clinvar id is 163253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7575273-CT-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0259 (21176/817948) while in subpopulation AMR AF= 0.0415 (925/22266). AF 95% confidence interval is 0.0393. There are 0 homozygotes in gnomad4_exome. There are 10511 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DSP	NM_004415.4 link	c.2437-11delT	intron_variant	Intron 17 of 23	ENST00000379802.8	NP_004406.2	P15924-1B4DKX6
DSP	NM_001319034.2 link	c.2437-11delT	intron_variant	Intron 17 of 23		NP_001305963.1	P15924-3B4DKX6
DSP	NM_001008844.3 link	c.2437-11delT	intron_variant	Intron 17 of 23		NP_001008844.1	P15924-2B4DKX6Q4LE79

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DSP	ENST00000379802.8 link	c.2437-21delT	intron_variant	Intron 17 of 23	1	NM_004415.4	ENSP00000369129.3	P15924-1
DSP	ENST00000418664.2 link	c.2437-21delT	intron_variant	Intron 17 of 23	1		ENSP00000396591.2	P15924-2
DSP	ENST00000710359.1 link	c.2437-21delT	intron_variant	Intron 17 of 23			ENSP00000518230.1
DSP	ENST00000684395.1 link	n.1078-21delT	intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

121

AN:

147218

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000951

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.00148

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000406

Gnomad OTH

AF:

0.000503

GnomAD4 exome

AF:

0.0259

AC:

21176

AN:

817948

Hom.:

Cov.:

AF XY:

0.0260

AC XY:

10511

AN XY:

403684

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.0415

Gnomad4 ASJ exome

AF:

0.0341

Gnomad4 EAS exome

AF:

0.0338

Gnomad4 SAS exome

AF:

0.0248

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.0243

Gnomad4 OTH exome

AF:

0.0294

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000923

AC:

136

AN:

147288

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

AN XY:

71670

show subpopulations

Gnomad4 AFR

AF:

0.00196

Gnomad4 AMR

AF:

0.000950

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000215

Gnomad4 FIN

AF:

0.00148

Gnomad4 NFE

AF:

0.000406

Gnomad4 OTH

AF:

0.000499

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 20, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2437-11delT in intron 17 of DSP: This variant is not expected to have clinical s ignificance because it has been identified in 18% (1498/8254) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS). -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy 2

Other:1

Institute of Human Genetics, University of Wuerzburg

Significance: not provided

Review Status: no classification provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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