chr6-7580585-T-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004415.4(DSP):c.4395T>G(p.Tyr1465Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y1465Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004415.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.4395T>G | p.Tyr1465Ter | stop_gained | 23/24 | ENST00000379802.8 | |
DSP | NM_001008844.3 | c.3582+813T>G | intron_variant | ||||
DSP | NM_001319034.2 | c.4050+345T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.4395T>G | p.Tyr1465Ter | stop_gained | 23/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.3582+813T>G | intron_variant | 1 | A2 | ||||
DSP | ENST00000710359.1 | c.4050+345T>G | intron_variant | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 9 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Heart Center, Academic Medical Center Amsterdam | Dec 01, 2018 | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 534281). This premature translational stop signal has been observed in individual(s) with DSP-related conditions (PMID: 25820315, 30345701, 30700137). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr1465*) in the DSP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSP are known to be pathogenic (PMID: 20716751, 24503780, 25227139). - |
Arrhythmogenic right ventricular dysplasia 8 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine | Oct 26, 2023 | The c.4395T>G (p.Tyr1465*) variant in the DSP gene introduces a premature translation termination codon at position 1465. This variant is predicted to result in an absent or disrupted protein product. This variant has been observed in individuals with arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy (DCM) (PMID: 25820315, 30345701, 30700137). Loss-of-function variants in DSP gene are known to be pathogenic (PMID: 20716751, 24503780, 25227139). This variant is not present in the general population according to gnomAD. Therefore, the c.4395T>G (p.Tyr1465*) variant in the DSP gene has been classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at