Variant 1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAA 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.738-7_738-5delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 1,340,408 control chromosomes in the GnomAD database, including 422 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 412 hom., cov: 0)

Exomes 𝑓: 0.10 ( 10 hom. )

Consequence

CASQ2
NM_001232.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.72

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-GAAA-G is Benign according to our data. Variant chr1-115725557-GAAA-G is described in ClinVar as [Benign]. Clinvar id is 522227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-115725557-GAAA-G is described in Lovd as [Benign]. Variant chr1-115725557-GAAA-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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.738-7_738-5delTTT		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.738-7_738-5delTTT		splice_region_variant, intron_variant		1	NM_001232.4	ENSP00000261448.5		O14958-1
CASQ2	ENST00000488931.2 linkuse as main transcript	n.110-7_110-5delTTT		splice_region_variant, intron_variant		3		ENSP00000518226.1

Frequencies

GnomAD3 genomes

AF:

0.0507

AC:

5782

AN:

113970

Hom.:

411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.00501

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.00395

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0163

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.0396

GnomAD4 exome

AF:

0.102

AC:

125489

AN:

1226468

Hom.:

AF XY:

0.102

AC XY:

62289

AN XY:

609708

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.0819

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.0873

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.0508

AC:

5793

AN:

113940

Hom.:

412

Cov.:

AF XY:

0.0517

AC XY:

2731

AN XY:

52840

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.0231

Gnomad4 ASJ

AF:

0.00501

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.00399

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.0395

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2019	- -

not specified

Benign:2

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	Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	Feb 11, 2020	- -

Catecholaminergic polymorphic ventricular tachycardia 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	May 04, 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

Jun 14, 2017

- -

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