rs397517394
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024422.6(DSC2):c.1552G>T(p.Val518Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. V518L) has been classified as Likely benign.
Frequency
Consequence
NM_024422.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.1552G>T | p.Val518Phe | missense_variant | 11/16 | ENST00000280904.11 | |
DSC2 | NM_004949.5 | c.1552G>T | p.Val518Phe | missense_variant | 11/17 | ||
DSC2 | NM_001406506.1 | c.1123G>T | p.Val375Phe | missense_variant | 11/16 | ||
DSC2 | NM_001406507.1 | c.1123G>T | p.Val375Phe | missense_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.1552G>T | p.Val518Phe | missense_variant | 11/16 | 1 | NM_024422.6 | P1 | |
DSC2 | ENST00000251081.8 | c.1552G>T | p.Val518Phe | missense_variant | 11/17 | 1 | |||
DSC2 | ENST00000648081.1 | c.1123G>T | p.Val375Phe | missense_variant | 12/17 | ||||
DSC2 | ENST00000682357.1 | c.1123G>T | p.Val375Phe | missense_variant | 11/16 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251108Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135704
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461620Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727092
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 07, 2023 | This missense variant replaces valine with phenylalanine at codon 518 of the DSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSC2-related disorders in the literature. This variant has been identified in 1/251108 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at