chr12-32869063-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001005242.3(PKP2):c.1035-1G>A variant causes a splice acceptor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001005242.3 splice_acceptor, intron
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 c.1035-1G>A variant in PKP2 has not been previously reported in individuals with ARVC or in large population studies. This variant occurs in the invariant r egion (+/-1,2) of the splice consensus sequence and is predicted to cause altere d splicing leading to an abnormal or absent protein. Splicing variants and other truncating variants in PKP2 are well-reported in individuals with ARVC (ARVD/C Genetic Variant Database, http://arvcdatabase.info; Human Gene Mutation Database ). In summary, although additional studies are required to fully establish its c linical significance, the c.1035-1G>A variant is likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at