NM_001232.4:c.578_580delTCAinsAC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001232.4(CASQ2):c.578_580delTCAinsAC(p.Ile193AsnfsTer17) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001232.4 frameshift, missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.578_580delTCAinsAC | p.Ile193AsnfsTer17 | frameshift_variant, missense_variant | Exon 5 of 11 | 1 | NM_001232.4 | ENSP00000261448.5 | ||
CASQ2 | ENST00000488931.2 | n.302_304delTCAinsAC | non_coding_transcript_exon_variant | Exon 6 of 13 | 3 | ENSP00000518226.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia Pathogenic:1
The Ile193fs variant in CASQ2 has not been reported in the literature nor previo usly identified by our laboratory. This frameshift variant is predicted to alter the protein?s amino acid sequence beginning at position 193 and lead to a prema ture termination codon 17 amino acids downstream. This alteration is then predic ted to lead to a truncated or absent protein. Homozygous or compound heterozygou s variants in CASQ2 are strongly associated with CPVT and include loss-of-functi on variants (Roux-Buisson 2011). In summary, the severity of the predicted impac t of the Ile193fs variant supports that it is likely pathogenic and combination with a second disease-causing variant in CASQ2 would result in CPVT. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at