chr6-7585537-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_004415.4(DSP):c.8275C>T(p.Arg2759Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2759H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.8275C>T | p.Arg2759Cys | missense_variant | 24/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.6946C>T | p.Arg2316Cys | missense_variant | 24/24 | ||
DSP | NM_001008844.3 | c.6478C>T | p.Arg2160Cys | missense_variant | 24/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.8275C>T | p.Arg2759Cys | missense_variant | 24/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.6478C>T | p.Arg2160Cys | missense_variant | 24/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.6946C>T | p.Arg2316Cys | missense_variant | 24/24 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135876
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461868Hom.: 0 Cov.: 37 AF XY: 0.00000688 AC XY: 5AN XY: 727236
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | ClinVar contains an entry for this variant (Variation ID: 465916). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2759 of the DSP protein (p.Arg2759Cys). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Feb 13, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at