Variant NM_001232.4:c.784-17T>A 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.784-17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,569,936 control chromosomes in the GnomAD database, including 252,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27671 hom., cov: 33)

Exomes 𝑓: 0.56 ( 225119 hom. )

Consequence

CASQ2
NM_001232.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.349

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=-0.82).

BP6

Variant 1-115717911-A-T is Benign according to our data. Variant chr1-115717911-A-T is described in ClinVar as [Benign]. Clinvar id is 257652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-115717911-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4 link	c.784-17T>A		intron_variant	Intron 7 of 10	ENST00000261448.6	NP_001223.2	O14958-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6 link	c.784-17T>A		intron_variant	Intron 7 of 10	1	NM_001232.4	ENSP00000261448.5		O14958-1
CASQ2	ENST00000488931.2 link	n.*156-17T>A		intron_variant	Intron 9 of 12	3		ENSP00000518226.1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

90944

AN:

151924

Hom.:

27632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.625

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.649

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.564

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.601

GnomAD3 exomes

AF:

0.580

AC:

145689

AN:

251066

Hom.:

42672

AF XY:

0.575

AC XY:

78076

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.696

Gnomad AMR exome

AF:

0.627

Gnomad ASJ exome

AF:

0.539

Gnomad EAS exome

AF:

0.640

Gnomad SAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.547

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.562

AC:

796475

AN:

1417894

Hom.:

225119

Cov.:

AF XY:

0.561

AC XY:

397419

AN XY:

708204

show subpopulations

Gnomad4 AFR exome

AF:

0.694

Gnomad4 AMR exome

AF:

0.624

Gnomad4 ASJ exome

AF:

0.534

Gnomad4 EAS exome

AF:

0.671

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.549

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

AF:

0.599

AC:

91037

AN:

152042

Hom.:

27671

Cov.:

AF XY:

0.601

AC XY:

44686

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.691

Gnomad4 AMR

AF:

0.608

Gnomad4 ASJ

AF:

0.539

Gnomad4 EAS

AF:

0.649

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.564

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.600

Alfa

AF:

0.484

Hom.:

2436

Bravo

AF:

0.609

Asia WGS

AF:

0.609

AC:

2121

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 2

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Catecholaminergic polymorphic ventricular tachycardia

Benign:1

Sep 23, 2022

Cohesion Phenomics

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 1

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

DANN

Benign

0.49

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