rs786205106
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001232.4(CASQ2):c.339_354delCCTGTATATTCTTAAG(p.Ser113ArgfsTer6) variant causes a frameshift 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001232.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.339_354delCCTGTATATTCTTAAG | p.Ser113ArgfsTer6 | frameshift_variant | Exon 3 of 11 | 1 | NM_001232.4 | ENSP00000261448.5 | ||
CASQ2 | ENST00000488931.2 | n.63_78delCCTGTATATTCTTAAG | non_coding_transcript_exon_variant | Exon 4 of 13 | 3 | ENSP00000518226.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 2 Pathogenic:2
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not provided Pathogenic:1
Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies in rat myocytes, showed the del16 mutation decreased the sarcoplasmic reticulum Ca2+ storing capacity and reduce the amplitude of calcium currents (PMID: 16908766); This variant is associated with the following publications: (PMID: 18469084, 16908766, 32693635) -
Catecholaminergic polymorphic ventricular tachycardia 1 Pathogenic:1
This sequence change creates a premature translational stop signal (p.Ser113Argfs*6) in the CASQ2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CASQ2 are known to be pathogenic (PMID: 12386154). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with catecholaminergic polymorphic ventricular tachycardia (PMID: 16908766). This variant is also known as G112+5X. ClinVar contains an entry for this variant (Variation ID: 17611). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at