6-7541635-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000418664(DSP):c.-281C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 461,774 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00022 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00066 ( 2 hom. )
Consequence
DSP
ENST00000418664 5_prime_UTR_premature_start_codon_gain
ENST00000418664 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.584
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 6-7541635-C-T is Benign according to our data. Variant chr6-7541635-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 369568.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000217 (33/152314) while in subpopulation EAS AF= 0.0062 (32/5162). AF 95% confidence interval is 0.00451. There are 1 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152202Hom.: 1 Cov.: 33
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GnomAD4 exome AF: 0.000662 AC: 205AN: 309460Hom.: 2 Cov.: 3 AF XY: 0.000615 AC XY: 99AN XY: 160876
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GnomAD4 genome AF: 0.000217 AC: 33AN: 152314Hom.: 1 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Lethal acantholytic epidermolysis bullosa Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Woolly hair-skin fragility syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Epidermolysis bullosa simplex due to plakophilin deficiency Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at