rs146029947
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_024422.6(DSC2):c.2314G>A(p.Val772Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024422.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.2314G>A | p.Val772Met | missense_variant | 15/16 | ENST00000280904.11 | |
DSC2 | NM_004949.5 | c.2314G>A | p.Val772Met | missense_variant | 15/17 | ||
DSC2 | NM_001406506.1 | c.1885G>A | p.Val629Met | missense_variant | 15/16 | ||
DSC2 | NM_001406507.1 | c.1885G>A | p.Val629Met | missense_variant | 15/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.2314G>A | p.Val772Met | missense_variant | 15/16 | 1 | NM_024422.6 | P1 | |
DSC2 | ENST00000251081.8 | c.2314G>A | p.Val772Met | missense_variant | 15/17 | 1 | |||
DSC2 | ENST00000648081.1 | c.1885G>A | p.Val629Met | missense_variant | 16/17 | ||||
DSC2 | ENST00000682357.1 | c.1885G>A | p.Val629Met | missense_variant | 15/16 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251102Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135702
GnomAD4 exome AF: 0.000168 AC: 246AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 117AN XY: 727230
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74302
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 17, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Reported in a cohort of individuals not selected for a history of arrhythmia, cardiomyopathy, or family history of sudden cardiac death who underwent exome analysis (Ng et al., 2013); clinical details were not provided; This variant is associated with the following publications: (PMID: 23861362) - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Arrhythmogenic right ventricular dysplasia 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 18, 2018 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 06, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Familial isolated arrhythmogenic right ventricular dysplasia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at