rs3811003

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD, AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
catecholaminergic polymorphic ventricular tachycardia 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CASQ2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 257653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4 link	c.939+23C>T		intron_variant	Intron 9 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.939+23C>T		intron_variant	Intron 9 of 10	1	NM_001232.4	ENSP00000261448.5		O14958-1

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

GnomAD2 exomes

AF:

0.346

AC:

86909

AN:

251060

AF XY:

0.338

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 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

African (AFR)

AF:

0.565

AC:

16994

AN:

30080

American (AMR)

AF:

0.364

AC:

16196

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

6914

AN:

25072

East Asian (EAS)

AF:

0.479

AC:

18614

AN:

38868

South Asian (SAS)

AF:

0.293

AC:

24276

AN:

82944

European-Finnish (FIN)

AF:

0.295

AC:

15740

AN:

53360

Middle Eastern (MID)

AF:

0.369

AC:

1965

AN:

5330

European-Non Finnish (NFE)

AF:

0.315

AC:

300031

AN:

953072

Other (OTH)

AF:

0.343

AC:

18715

AN:

54640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

13545

27090

40636

54181

67726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9444

18888

28332

37776

47220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.389

AC:

59194

AN:

152146

Hom.:

12731

Cov.:

AF XY:

0.388

AC XY:

28861

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.564

AC:

23386

AN:

41488

American (AMR)

AF:

0.336

AC:

5137

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1006

AN:

3468

East Asian (EAS)

AF:

0.510

AC:

2629

AN:

5158

South Asian (SAS)

AF:

0.292

AC:

1408

AN:

4828

European-Finnish (FIN)

AF:

0.316

AC:

3346

AN:

10592

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

21024

AN:

68004

Other (OTH)

AF:

0.370

AC:

782

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1805

3610

5415

7220

9025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.337

Hom.:

25112

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

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 26, 2018

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 2

Benign:1

Apr 11, 2023

Genome-Nilou Lab

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

-0.79

CADD

Benign

2.0

(source)

DANN

Benign

0.77

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over