rs181769947
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1
The ENST00000261448.6(CASQ2):āc.774T>Cā(p.Phe258=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000964 in 1,607,516 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.00010 ( 0 hom., cov: 31)
Exomes š: 0.000096 ( 0 hom. )
Consequence
CASQ2
ENST00000261448.6 synonymous
ENST00000261448.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.39
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 -13 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 1-115725517-A-G is Benign according to our data. Variant chr1-115725517-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 392826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-115725517-A-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=2.39 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000101 (15/147866) while in subpopulation EAS AF= 0.0022 (11/5008). AF 95% confidence interval is 0.00123. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASQ2 | NM_001232.4 | c.774T>C | p.Phe258= | synonymous_variant | 7/11 | ENST00000261448.6 | NP_001223.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.774T>C | p.Phe258= | synonymous_variant | 7/11 | 1 | NM_001232.4 | ENSP00000261448 | P1 | |
CASQ2 | ENST00000488931.2 | c.*146T>C | 3_prime_UTR_variant, NMD_transcript_variant | 9/13 | 3 | ENSP00000518226 |
Frequencies
GnomAD3 genomes AF: 0.000102 AC: 15AN: 147766Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000219 AC: 55AN: 250572Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135402
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GnomAD4 exome AF: 0.0000959 AC: 140AN: 1459650Hom.: 0 Cov.: 42 AF XY: 0.000102 AC XY: 74AN XY: 726236
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GnomAD4 genome AF: 0.000101 AC: 15AN: 147866Hom.: 0 Cov.: 31 AF XY: 0.000125 AC XY: 9AN XY: 71768
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | CASQ2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Catecholaminergic polymorphic ventricular tachycardia 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 17, 2019 | 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
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Name
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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