18-31080180-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_024422.6(DSC2):āc.1436G>Cā(p.Arg479Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R479L) has been classified as Uncertain significance.
Frequency
Consequence
NM_024422.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.1436G>C | p.Arg479Pro | missense_variant | 10/16 | ENST00000280904.11 | |
DSC2 | NM_004949.5 | c.1436G>C | p.Arg479Pro | missense_variant | 10/17 | ||
DSC2 | NM_001406506.1 | c.1007G>C | p.Arg336Pro | missense_variant | 10/16 | ||
DSC2 | NM_001406507.1 | c.1007G>C | p.Arg336Pro | missense_variant | 10/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.1436G>C | p.Arg479Pro | missense_variant | 10/16 | 1 | NM_024422.6 | P1 | |
DSC2 | ENST00000251081.8 | c.1436G>C | p.Arg479Pro | missense_variant | 10/17 | 1 | |||
DSC2 | ENST00000648081.1 | c.1007G>C | p.Arg336Pro | missense_variant | 11/17 | ||||
DSC2 | ENST00000682357.1 | c.1007G>C | p.Arg336Pro | missense_variant | 10/16 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152046Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251214Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135774
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461824Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727210
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152046Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74266
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 17, 2020 | Variant summary: DSC2 c.1436G>C (p.Arg479Pro) results in a non-conservative amino acid change located in the Cadherin-like (IPR002126) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251214 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1436G>C in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at