rs7413162
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001232.4(CASQ2):c.1185C>T(p.Asp395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,592,320 control chromosomes in the GnomAD database, including 108,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.40 ( 12002 hom., cov: 31)
Exomes 𝑓: 0.37 ( 96016 hom. )
Consequence
CASQ2
NM_001232.4 synonymous
NM_001232.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.80
Genes affected
CASQ2 (HGNC:1513): (calsequestrin 2) The protein encoded by this gene specifies the cardiac muscle family member of the calsequestrin family. Calsequestrin is localized to the sarcoplasmic reticulum in cardiac and slow skeletal muscle cells. The protein is a calcium binding protein that stores calcium for muscle function. Mutations in this gene cause stress-induced polymorphic ventricular tachycardia, also referred to as catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2), a disease characterized by bidirectional ventricular tachycardia that may lead to cardiac arrest. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 1-115701256-G-A is Benign according to our data. Variant chr1-115701256-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 44157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-115701256-G-A is described in Lovd as [Pathogenic]. Variant chr1-115701256-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.8 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASQ2 | NM_001232.4 | c.1185C>T | p.Asp395= | synonymous_variant | 11/11 | ENST00000261448.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.1185C>T | p.Asp395= | synonymous_variant | 11/11 | 1 | NM_001232.4 | P1 | |
CASQ2 | ENST00000488931.2 | c.*557C>T | 3_prime_UTR_variant, NMD_transcript_variant | 13/13 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.397 AC: 59905AN: 150950Hom.: 11979 Cov.: 31
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GnomAD3 exomes AF: 0.381 AC: 95474AN: 250554Hom.: 18321 AF XY: 0.380 AC XY: 51479AN XY: 135384
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GnomAD4 exome AF: 0.367 AC: 529264AN: 1441250Hom.: 96016 Cov.: 30 AF XY: 0.368 AC XY: 264296AN XY: 717728
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GnomAD4 genome ? AF: 0.397 AC: 59982AN: 151070Hom.: 12002 Cov.: 31 AF XY: 0.401 AC XY: 29642AN XY: 73838
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:16
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 10, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 09, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | May 28, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Catecholaminergic polymorphic ventricular tachycardia 2 Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Catecholaminergic polymorphic ventricular tachycardia Benign:2
Likely benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Caudal regression sequence Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Neural tube defect Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2015 | This alteration is classified as 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
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at