rs548536938
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000261448.6(CASQ2):āc.893A>Gā(p.Asn298Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N298K) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000261448.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASQ2 | NM_001232.4 | c.893A>G | p.Asn298Ser | missense_variant | 9/11 | ENST00000261448.6 | NP_001223.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.893A>G | p.Asn298Ser | missense_variant | 9/11 | 1 | NM_001232.4 | ENSP00000261448 | P1 | |
CASQ2 | ENST00000488931.2 | c.*265A>G | 3_prime_UTR_variant, NMD_transcript_variant | 11/13 | 3 | ENSP00000518226 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251372Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135854
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461760Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727182
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74452
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1;C2677794:Catecholaminergic polymorphic ventricular tachycardia 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 19, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 11, 2024 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has been observed in an individual with DCM (PMID: 31983221); This variant is associated with the following publications: (PMID: 31983221) - |
Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 12, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 298 of the CASQ2 protein (p.Asn298Ser). This variant is present in population databases (rs548536938, gnomAD 0.02%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). ClinVar contains an entry for this variant (Variation ID: 519436). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CASQ2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 27, 2024 | This alteration is classified as likely 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at