rs369821143
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004415.4(DSP):c.2131-10T>C 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 0.00000372 in 1,613,870 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
DSP
NM_004415.4 splice_polypyrimidine_tract, intron
NM_004415.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.002102
2
Clinical Significance
Conservation
PhyloP100: 0.0780
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
Variant 6-7574076-T-C is Benign according to our data. Variant chr6-7574076-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 178029.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.2131-10T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000379802.8 | |||
DSP | NM_001008844.3 | c.2131-10T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
DSP | NM_001319034.2 | c.2131-10T>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.2131-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004415.4 | P2 | |||
DSP | ENST00000418664.2 | c.2131-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | A2 | ||||
DSP | ENST00000710359.1 | c.2131-10T>C | splice_polypyrimidine_tract_variant, intron_variant | A2 | |||||
DSP | ENST00000684395.1 | n.772-10T>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251226Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135780
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461652Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727124
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74372
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 22, 2014 | The 2131-10T>C variant in DSP has not been reported in individuals with cardiomy opathy, but has been identified in 3/4406 of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; rs369821143). This variant is located in the 3' splice region. Computational tools do not sug gest an impact to splicing. However, this information is not predictive enough t o rule out pathogenicity. Additional information is needed to fully assess the c linical significance of the 2131-10T>C variant. - |
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 | May 16, 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 11, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at