rs140488069
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_004415.4(DSP):c.1155G>A(p.Ala385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,756 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: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000067 ( 0 hom. )
Consequence
DSP
NM_004415.4 synonymous
NM_004415.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.40
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=-0.85).
BP6
?
Variant 6-7567795-G-A is Benign according to our data. Variant chr6-7567795-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 378907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.4 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.1155G>A | p.Ala385= | synonymous_variant | 10/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.1155G>A | p.Ala385= | synonymous_variant | 10/24 | ||
DSP | NM_001008844.3 | c.1155G>A | p.Ala385= | synonymous_variant | 10/24 | ||
DSP | NM_001406591.1 | c.1155G>A | p.Ala385= | synonymous_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.1155G>A | p.Ala385= | synonymous_variant | 10/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.1155G>A | p.Ala385= | synonymous_variant | 10/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.1155G>A | p.Ala385= | synonymous_variant | 10/24 | A2 | |||
DSP | ENST00000682228.1 | n.810G>A | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152004Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251194Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135770
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GnomAD4 exome AF: 0.0000670 AC: 98AN: 1461636Hom.: 0 Cov.: 34 AF XY: 0.0000605 AC XY: 44AN XY: 727126
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152120Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 13, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 26, 2015 | This 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. - |
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 | Dec 18, 2023 | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 30, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2021 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 05, 2020 | 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. - |
Woolly hair-skin fragility syndrome;C1843896:Arrhythmogenic right ventricular dysplasia 8;C1852127:Keratosis palmoplantaris striata 2;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma;C1864826:Lethal acantholytic epidermolysis bullosa;C4014393:Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 14, 2021 | - - |
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