rs200265771

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001232.4(CASQ2):c.752G>A(p.Arg251His) variant causes a missense change. The variant allele was found at a frequency of 0.0000296 in 1,420,292 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R251C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CASQ2
NM_001232.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:9

Conservation

PhyloP100: 5.17

Publications

3 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: AR, AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
catecholaminergic polymorphic ventricular tachycardia 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ2	NM_001232.4	MANE Select	c.752G>A	p.Arg251His	missense	Exon 7 of 11	NP_001223.2	O14958-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CASQ2	ENST00000261448.6	TSL:1 MANE Select	c.752G>A	p.Arg251His	missense	Exon 7 of 11	ENSP00000261448.5	O14958-1
CASQ2	ENST00000713711.1		c.893G>A	p.Arg298His	missense	Exon 8 of 12	ENSP00000519014.1	A0AAQ5BGS1
CASQ2	ENST00000874189.1		c.752G>A	p.Arg251His	missense	Exon 7 of 10	ENSP00000544248.1

Frequencies

GnomAD3 genomes

AF:

0.0000402

AC:

AN:

124388

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000232

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000317

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000323

AC:

AN:

247550

AF XY:

0.0000299

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1295904

Hom.:

Cov.:

AF XY:

0.0000353

AC XY:

AN XY:

651680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30280

American (AMR)

AF:

0.000114

AC:

AN:

44008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24780

East Asian (EAS)

AF:

0.000105

AC:

AN:

38270

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4370

European-Non Finnish (NFE)

AF:

0.0000249

AC:

AN:

965034

Other (OTH)

AF:

0.0000551

AC:

AN:

54442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000402

AC:

AN:

124388

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

57952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31408

American (AMR)

AF:

0.000203

AC:

AN:

9872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3328

East Asian (EAS)

AF:

0.000232

AC:

AN:

4308

South Asian (SAS)

AF:

0.00

AC:

AN:

3972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0000317

AC:

AN:

63162

Other (OTH)

AF:

0.00

AC:

AN:

1592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Catecholaminergic polymorphic ventricular tachycardia 2 (3)

Cardiovascular phenotype (2)

not provided (2)

Catecholaminergic polymorphic ventricular tachycardia 1 (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.5

PhyloP100

5.2

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.49

MVP

0.94

MPC

0.20

ClinPred

0.45

GERP RS

5.3

Varity_R

0.73

gMVP

0.51

Mutation Taster

=41/59

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over