Variant chr1-115725557-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001232.4(CASQ2):c.738-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 319 hom., cov: 0)

Exomes 𝑓: 0.035 ( 79 hom. )

Consequence

CASQ2
NM_001232.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.516

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-115725557-G-GA is Benign according to our data. Variant chr1-115725557-G-GA is described in ClinVar as [Benign]. Clinvar id is 915585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 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.738-5dupT		splice_region_variant, intron_variant		ENST00000261448.6	NP_001223.2	O14958-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6 linkuse as main transcript	c.738-5dupT		splice_region_variant, intron_variant		1	NM_001232.4	ENSP00000261448.5		O14958-1
CASQ2	ENST00000488931.2 linkuse as main transcript	n.*110-5dupT		splice_region_variant, intron_variant		3		ENSP00000518226.1

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

5925

AN:

113780

Hom.:

319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0901

Gnomad ASJ

AF:

0.000669

Gnomad EAS

AF:

0.0643

Gnomad SAS

AF:

0.00700

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.0395

GnomAD4 exome

AF:

0.0349

AC:

44129

AN:

1264726

Hom.:

Cov.:

AF XY:

0.0348

AC XY:

21900

AN XY:

629560

show subpopulations

Gnomad4 AFR exome

AF:

0.0787

Gnomad4 AMR exome

AF:

0.0736

Gnomad4 ASJ exome

AF:

0.0475

Gnomad4 EAS exome

AF:

0.0409

Gnomad4 SAS exome

AF:

0.0463

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.0311

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0521

AC:

5930

AN:

113752

Hom.:

319

Cov.:

AF XY:

0.0541

AC XY:

2854

AN XY:

52764

show subpopulations

Gnomad4 AFR

AF:

0.145

Gnomad4 AMR

AF:

0.0901

Gnomad4 ASJ

AF:

0.000669

Gnomad4 EAS

AF:

0.0642

Gnomad4 SAS

AF:

0.00675

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.00259

Gnomad4 OTH

AF:

0.0395

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Nov 26, 2019

- -

Catecholaminergic polymorphic ventricular tachycardia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Catecholaminergic polymorphic ventricular tachycardia 1;C2677794:Catecholaminergic polymorphic ventricular tachycardia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 17, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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