Variant rs3811003 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001232.4(CASQ2):c.939+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,440,028 control chromosomes in the GnomAD database, including 83,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12731 hom., cov: 33)

Exomes 𝑓: 0.33 ( 71065 hom. )

Consequence

CASQ2
NM_001232.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.198

Variant links:

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]

CASQ2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-115705169-G-A is Benign according to our data. Variant chr1-115705169-G-A is described in ClinVar as [Benign]. Clinvar id is 257653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-115705169-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASQ2	NM_001232.4 linkuse as main transcript	c.939+23C>T		intron_variant		ENST00000261448.6	NP_001223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6 linkuse as main transcript	c.939+23C>T		intron_variant		1	NM_001232.4	ENSP00000261448	P1	O14958-1
CASQ2	ENST00000488931.2 linkuse as main transcript	c.*311+23C>T		intron_variant, NMD_transcript_variant		3		ENSP00000518226

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

59140

AN:

152026

Hom.:

12719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.564

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.346

AC:

86909

AN:

251060

Hom.:

15992

AF XY:

0.338

AC XY:

45886

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.569

Gnomad AMR exome

AF:

0.366

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.520

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.298

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

AF:

0.326

AC:

419445

AN:

1287882

Hom.:

71065

Cov.:

AF XY:

0.323

AC XY:

210046

AN XY:

650278

show subpopulations

Gnomad4 AFR exome

AF:

0.565

Gnomad4 AMR exome

AF:

0.364

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.295

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

AF:

0.389

AC:

59194

AN:

152146

Hom.:

12731

Cov.:

AF XY:

0.388

AC XY:

28861

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.564

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.290

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.316

Gnomad4 NFE

AF:

0.309

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.322

Hom.:

14313

Bravo

AF:

0.401

Asia WGS

AF:

0.381

AC:

1328

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Catecholaminergic polymorphic ventricular tachycardia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over