rs11558732
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004415.4(DSP):c.*9T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 1,612,636 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0063 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0082 ( 69 hom. )
Consequence
DSP
NM_004415.4 3_prime_UTR
NM_004415.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.08
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 6-7585887-T-A is Benign according to our data. Variant chr6-7585887-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 44850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7585887-T-A is described in Lovd as [Benign]. Variant chr6-7585887-T-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0063 (959/152330) while in subpopulation NFE AF= 0.009 (612/68020). AF 95% confidence interval is 0.00841. There are 6 homozygotes in gnomad4. There are 437 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.*9T>A | 3_prime_UTR_variant | 24/24 | ENST00000379802.8 | ||
DSP | NM_001008844.3 | c.*9T>A | 3_prime_UTR_variant | 24/24 | |||
DSP | NM_001319034.2 | c.*9T>A | 3_prime_UTR_variant | 24/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.*9T>A | 3_prime_UTR_variant | 24/24 | 1 | NM_004415.4 | P2 | ||
DSP | ENST00000418664.2 | c.*9T>A | 3_prime_UTR_variant | 24/24 | 1 | A2 | |||
DSP | ENST00000710359.1 | c.*9T>A | 3_prime_UTR_variant | 24/24 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00631 AC: 960AN: 152212Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00596 AC: 1485AN: 248956Hom.: 9 AF XY: 0.00572 AC XY: 772AN XY: 134974
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GnomAD4 exome AF: 0.00818 AC: 11944AN: 1460306Hom.: 69 Cov.: 31 AF XY: 0.00795 AC XY: 5779AN XY: 726536
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GnomAD4 genome ? AF: 0.00630 AC: 959AN: 152330Hom.: 6 Cov.: 32 AF XY: 0.00587 AC XY: 437AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:12
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 16, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | DSP: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 09, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 28, 2018 | This variant is associated with the following publications: (PMID: 21723241, 26332594) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 20, 2012 | *9T>A variant in 3' UTR of DSP: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and it has been ident ified in 1.11% (78/7020) of European American chromosomes by the NHLBI Exome Seq uencing Project in a broad population (http://evs.gs.washington.edu/EVS; rs11558 732). - |
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 18, 2015 | - - |
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jun 05, 2015 | - - |
Lethal acantholytic epidermolysis bullosa Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 26, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Woolly hair-skin fragility syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 26, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Arrhythmogenic right ventricular dysplasia 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 26, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at