Variant 1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAA 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.738-5delT 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 0.028 ( 51 hom., cov: 0)

Exomes 𝑓: 0.13 ( 14 hom. )

Consequence

CASQ2
NM_001232.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

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-GA-G is Benign according to our data. Variant chr1-115725557-GA-G is described in ClinVar as [Benign]. Clinvar id is 522226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-115725557-GA-G is described in Lovd as [Benign]. Variant chr1-115725557-GA-G is described in Lovd as [Benign]. Variant chr1-115725557-GA-G is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4 link	c.738-5delT		splice_region_variant, intron_variant	Intron 6 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.738-5delT		splice_region_variant, intron_variant	Intron 6 of 10	1	NM_001232.4	ENSP00000261448.5		O14958-1
CASQ2	ENST00000488931.2 link	n.*110-5delT		splice_region_variant, intron_variant	Intron 8 of 12	3		ENSP00000518226.1

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

3233

AN:

113974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.00260

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.00669

Gnomad EAS

AF:

0.00523

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.00624

Gnomad MID

AF:

0.0122

Gnomad NFE

AF:

0.0260

Gnomad OTH

AF:

0.0227

GnomAD4 exome

AF:

0.132

AC:

164324

AN:

1244766

Hom.:

Cov.:

AF XY:

0.128

AC XY:

79523

AN XY:

619174

show subpopulations

Gnomad4 AFR exome

AF:

0.0884

Gnomad4 AMR exome

AF:

0.0762

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.0952

Gnomad4 SAS exome

AF:

0.0885

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.0284

AC:

3235

AN:

113944

Hom.:

Cov.:

AF XY:

0.0281

AC XY:

1486

AN XY:

52850

show subpopulations

Gnomad4 AFR

AF:

0.0456

Gnomad4 AMR

AF:

0.0215

Gnomad4 ASJ

AF:

0.00669

Gnomad4 EAS

AF:

0.00525

Gnomad4 SAS

AF:

0.00951

Gnomad4 FIN

AF:

0.00624

Gnomad4 NFE

AF:

0.0260

Gnomad4 OTH

AF:

0.0226

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Dec 08, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Sep 06, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

CASQ2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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