rs148743859
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_004415.4(DSP):āc.6351T>Cā(p.Asp2117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,614,062 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 (ā ā ).
Frequency
Genomes: š 0.00018 ( 0 hom., cov: 32)
Exomes š: 0.00015 ( 0 hom. )
Consequence
DSP
NM_004415.4 synonymous
NM_004415.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.295
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 6-7583613-T-C is Benign according to our data. Variant chr6-7583613-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 163283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7583613-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.295 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.6351T>C | p.Asp2117= | synonymous_variant | 24/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.5022T>C | p.Asp1674= | synonymous_variant | 24/24 | ||
DSP | NM_001008844.3 | c.4554T>C | p.Asp1518= | synonymous_variant | 24/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.6351T>C | p.Asp2117= | synonymous_variant | 24/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.4554T>C | p.Asp1518= | synonymous_variant | 24/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.5022T>C | p.Asp1674= | synonymous_variant | 24/24 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251352Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135882
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GnomAD4 exome AF: 0.000146 AC: 214AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 98AN XY: 727246
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GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74342
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cardiomyopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 16, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Dec 09, 2020 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 09, 2016 | Variant summary: The DSP c.6351T>C (p.Asp2117Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. This variant was found in 11/121018 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0001653 (11/66564). This frequency is about 17 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. In addition, one clinical diagnostic laboratories/reputable databases has classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Due to the synonymous nature of this variant, the lack of predicted effect on splicing, and the relatively high frequency in the normal population, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | Asp2117Asp in exon 24 of DSP: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 3/7020 European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs148743859). Asp2117Asp in exon 24 of DSP (rs148743859; allele frequency = 0.04%, 3/7020) ** - |
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
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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