chr12-32877904-C-CGGCCGCCT
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001005242.3(PKP2):c.968_975dupAGGCGGCC(p.Ala326ArgfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A325A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001005242.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular cardiomyopathy Pathogenic:1
The p.Ala326fs variant in PKP2 has not been previously reported in individuals w ith ARVC or in large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a fr ameshift, which alters the protein?s amino acid sequence beginning at position 3 26 and leads to a premature termination codon 29 amino acids downstream. This al teration is then predicted to lead to a truncated or absent protein. In summary, although additional studies are required to fully establish its clinical signif icance, the p.Ala326fs variant is likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at