chr6-7576284-T-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_004415.4(DSP):c.2631-10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,460,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
DSP
NM_004415.4 intron
NM_004415.4 intron
Scores
2
Splicing: ADA: 0.001452
2
Clinical Significance
Conservation
PhyloP100: 0.306
Publications
0 publications found
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 Gene-Disease associations (from GenCC):
- arrhythmogenic right ventricular dysplasia 8Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- keratosis palmoplantaris striata 2Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Genomics England PanelApp
- skin fragility-woolly hair-palmoplantar keratoderma syndromeInheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Genomics England PanelApp, Ambry Genetics
- arrhythmogenic cardiomyopathy with wooly hair and keratodermaInheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen, Orphanet, Ambry Genetics
- cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesisInheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
- lethal acantholytic epidermolysis bullosaInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- striate palmoplantar keratodermaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- severe dermatitis-multiple allergies-metabolic wasting syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 6-7576284-T-A is Benign according to our data. Variant chr6-7576284-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 465888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.2631-10T>A | intron_variant | Intron 18 of 23 | ENST00000379802.8 | NP_004406.2 | ||
DSP | NM_001319034.2 | c.2631-10T>A | intron_variant | Intron 18 of 23 | NP_001305963.1 | |||
DSP | NM_001008844.3 | c.2631-10T>A | intron_variant | Intron 18 of 23 | NP_001008844.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 250960 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250960
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1460808Hom.: 0 Cov.: 28 AF XY: 0.0000151 AC XY: 11AN XY: 726776 show subpopulations
GnomAD4 exome
AF:
AC:
23
AN:
1460808
Hom.:
Cov.:
28
AF XY:
AC XY:
11
AN XY:
726776
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
0
AN:
39668
South Asian (SAS)
AF:
AC:
0
AN:
86216
European-Finnish (FIN)
AF:
AC:
0
AN:
53386
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
23
AN:
1111102
Other (OTH)
AF:
AC:
0
AN:
60364
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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2
4
6
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10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
May 21, 2019
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Jul 01, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Cardiomyopathy Benign:1
Oct 25, 2018
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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