rs1296848321
Variant names:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_004415.4(DSP):c.7185C>T(p.Gly2395Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,008 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
DSP
NM_004415.4 synonymous
NM_004415.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.428
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=-0.57).
BP6
Variant 6-7584447-C-T is Benign according to our data. Variant chr6-7584447-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 534331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.428 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.7185C>T | p.Gly2395Gly | synonymous_variant | Exon 24 of 24 | ENST00000379802.8 | NP_004406.2 | |
DSP | NM_001319034.2 | c.5856C>T | p.Gly1952Gly | synonymous_variant | Exon 24 of 24 | NP_001305963.1 | ||
DSP | NM_001008844.3 | c.5388C>T | p.Gly1796Gly | synonymous_variant | Exon 24 of 24 | NP_001008844.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.7185C>T | p.Gly2395Gly | synonymous_variant | Exon 24 of 24 | 1 | NM_004415.4 | ENSP00000369129.3 | ||
DSP | ENST00000418664.2 | c.5388C>T | p.Gly1796Gly | synonymous_variant | Exon 24 of 24 | 1 | ENSP00000396591.2 | |||
DSP | ENST00000710359.1 | c.5856C>T | p.Gly1952Gly | synonymous_variant | Exon 24 of 24 | ENSP00000518230.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251450Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135898
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461888Hom.: 0 Cov.: 36 AF XY: 0.00000963 AC XY: 7AN XY: 727242
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Oct 30, 2023
All of Us Research Program, National Institutes of Health
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
May 12, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Cardiomyopathy Benign:1
Nov 30, 2018
Color Diagnostics, LLC DBA Color Health
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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not provided Benign:1
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Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided
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Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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