rs113028223
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_004415.4(DSP):c.423-16_423-15insC variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 1,613,606 control chromosomes in the GnomAD database, including 391 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.028 ( 190 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 201 hom. )
Consequence
DSP
NM_004415.4 splice_polypyrimidine_tract, intron
NM_004415.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.261
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 -16 ACMG points.
BP6
Variant 6-7559210-G-GC is Benign according to our data. Variant chr6-7559210-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 44902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.423-16_423-15insC | splice_polypyrimidine_tract_variant, intron_variant | ENST00000379802.8 | |||
DSP | NM_001008844.3 | c.423-16_423-15insC | splice_polypyrimidine_tract_variant, intron_variant | ||||
DSP | NM_001319034.2 | c.423-16_423-15insC | splice_polypyrimidine_tract_variant, intron_variant | ||||
DSP | NM_001406591.1 | c.423-16_423-15insC | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.423-16_423-15insC | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004415.4 | P2 | |||
DSP | ENST00000418664.2 | c.423-16_423-15insC | splice_polypyrimidine_tract_variant, intron_variant | 1 | A2 | ||||
DSP | ENST00000710359.1 | c.423-16_423-15insC | splice_polypyrimidine_tract_variant, intron_variant | A2 | |||||
DSP | ENST00000683563.1 | n.315-16_315-15insC | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0280 AC: 4254AN: 152090Hom.: 180 Cov.: 32
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GnomAD3 exomes AF: 0.00800 AC: 1994AN: 249314Hom.: 103 AF XY: 0.00635 AC XY: 858AN XY: 135108
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GnomAD4 exome AF: 0.00315 AC: 4607AN: 1461398Hom.: 201 Cov.: 31 AF XY: 0.00288 AC XY: 2093AN XY: 726960
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GnomAD4 genome AF: 0.0282 AC: 4291AN: 152208Hom.: 190 Cov.: 32 AF XY: 0.0277 AC XY: 2060AN XY: 74422
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 24, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 23, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 22, 2016 | Variant summary: The DSP c.423-16_423-15insC variant involves the insetion of an intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 1200/120544 control chromosomes (58 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.1054381 (1047/9930). This frequency is about 4217 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign. - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Cardiomyopathy Benign:1
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
Computational scores
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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