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GeneBe

6-7578586-T-G

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+24T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,576,868 control chromosomes in the GnomAD database, including 485,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43290 hom., cov: 31)
Exomes 𝑓: 0.79 ( 442428 hom. )

Consequence

DSP
NM_004415.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.0270
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]

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=-0.84).
BP6
Variant 6-7578586-T-G is Benign according to our data. Variant chr6-7578586-T-G is described in ClinVar as [Benign]. Clinvar id is 259383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7578586-T-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DSPNM_004415.4 linkuse as main transcriptc.3084+24T>G intron_variant ENST00000379802.8
DSPNM_001008844.3 linkuse as main transcriptc.3084+24T>G intron_variant
DSPNM_001319034.2 linkuse as main transcriptc.3084+24T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DSPENST00000379802.8 linkuse as main transcriptc.3084+24T>G intron_variant 1 NM_004415.4 P2P15924-1
DSPENST00000418664.2 linkuse as main transcriptc.3084+24T>G intron_variant 1 A2P15924-2
DSPENST00000710359.1 linkuse as main transcriptc.3084+24T>G intron_variant A2

Frequencies

GnomAD3 genomes
AF:
0.752
AC:
113963
AN:
151468
Hom.:
43271
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.656
Gnomad AMI
AF:
0.863
Gnomad AMR
AF:
0.797
Gnomad ASJ
AF:
0.824
Gnomad EAS
AF:
0.797
Gnomad SAS
AF:
0.748
Gnomad FIN
AF:
0.715
Gnomad MID
AF:
0.815
Gnomad NFE
AF:
0.797
Gnomad OTH
AF:
0.780
GnomAD3 exomes
AF:
0.776
AC:
193921
AN:
249964
Hom.:
75402
AF XY:
0.778
AC XY:
105099
AN XY:
135100
show subpopulations
Gnomad AFR exome
AF:
0.654
Gnomad AMR exome
AF:
0.786
Gnomad ASJ exome
AF:
0.817
Gnomad EAS exome
AF:
0.803
Gnomad SAS exome
AF:
0.743
Gnomad FIN exome
AF:
0.720
Gnomad NFE exome
AF:
0.801
Gnomad OTH exome
AF:
0.785
GnomAD4 exome
AF:
0.787
AC:
1121668
AN:
1425284
Hom.:
442428
Cov.:
23
AF XY:
0.787
AC XY:
559805
AN XY:
711420
show subpopulations
Gnomad4 AFR exome
AF:
0.644
Gnomad4 AMR exome
AF:
0.791
Gnomad4 ASJ exome
AF:
0.814
Gnomad4 EAS exome
AF:
0.813
Gnomad4 SAS exome
AF:
0.747
Gnomad4 FIN exome
AF:
0.720
Gnomad4 NFE exome
AF:
0.796
Gnomad4 OTH exome
AF:
0.785
GnomAD4 genome
AF:
0.752
AC:
114033
AN:
151584
Hom.:
43290
Cov.:
31
AF XY:
0.751
AC XY:
55630
AN XY:
74082
show subpopulations
Gnomad4 AFR
AF:
0.656
Gnomad4 AMR
AF:
0.797
Gnomad4 ASJ
AF:
0.824
Gnomad4 EAS
AF:
0.797
Gnomad4 SAS
AF:
0.749
Gnomad4 FIN
AF:
0.715
Gnomad4 NFE
AF:
0.797
Gnomad4 OTH
AF:
0.775
Alfa
AF:
0.772
Hom.:
8509
Bravo
AF:
0.756

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
Lethal acantholytic epidermolysis bullosa Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
Woolly hair-skin fragility syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 15, 2018This 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
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
3.2
Dann
Benign
0.50
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.

Other links and lift over

dbSNP: rs2806229; hg19: chr6-7578819; COSMIC: COSV65791251; API