rs560969680
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_004415.4(DSP):c.1806T>C(p.Asp602=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,614,224 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 1 hom. )
Consequence
DSP
NM_004415.4 synonymous
NM_004415.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.544
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=-0.52).
BP6
?
Variant 6-7571487-T-C is Benign according to our data. Variant chr6-7571487-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 465884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-7571487-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.544 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.1806T>C | p.Asp602= | synonymous_variant | 14/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.1806T>C | p.Asp602= | synonymous_variant | 14/24 | ||
DSP | NM_001008844.3 | c.1806T>C | p.Asp602= | synonymous_variant | 14/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.1806T>C | p.Asp602= | synonymous_variant | 14/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.1806T>C | p.Asp602= | synonymous_variant | 14/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.1806T>C | p.Asp602= | synonymous_variant | 14/24 | A2 | |||
DSP | ENST00000684395.1 | n.190T>C | non_coding_transcript_exon_variant | 2/5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000123 AC: 31AN: 251280Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135800
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GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461894Hom.: 1 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 727248
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 03, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 14, 2017 | 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. - |
DSP-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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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