rs150722502

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_201596.3(CACNB2):c.209G>A(p.Arg70His) variant causes a missense change. The variant allele was found at a frequency of 0.000973 in 1,568,760 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00099 ( 1 hom. )

Consequence

CACNB2
NM_201596.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 7.14

Publications

7 publications found

Variant links:

Genes affected

CACNB2 (HGNC:1402): (calcium voltage-gated channel auxiliary subunit beta 2) This gene encodes a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome, an autoimmune disorder. Mutations in this gene are associated with Brugada syndrome. Alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Feb 2013]

CACNB2 Gene-Disease associations (from GenCC):

Brugada syndrome 4
Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Laboratory for Molecular Medicine
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
short QT syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CACNB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045506954).

BP6

Variant 10-18150971-G-A is Benign according to our data. Variant chr10-18150971-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 190713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 109 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.209G>A	p.Arg70His	missense_variant	Exon 2 of 14	ENST00000324631.13	NP_963890.2	Q08289-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 link	c.209G>A	p.Arg70His	missense_variant	Exon 2 of 14	1	NM_201596.3	ENSP00000320025.8		Q08289-1

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

109

AN:

144244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000579

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000594

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000773

AC:

194

AN:

251022

AF XY:

0.000833

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000995

AC:

1417

AN:

1424406

Hom.:

Cov.:

AF XY:

0.000991

AC XY:

703

AN XY:

709514

show subpopulations

African (AFR)

AF:

0.0000924

AC:

AN:

32478

American (AMR)

AF:

0.000114

AC:

AN:

44022

Ashkenazi Jewish (ASJ)

AF:

0.000197

AC:

AN:

25372

East Asian (EAS)

AF:

0.0000801

AC:

AN:

37454

South Asian (SAS)

AF:

0.0000467

AC:

AN:

85596

European-Finnish (FIN)

AF:

0.000701

AC:

AN:

51358

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.00121

AC:

1312

AN:

1084046

Other (OTH)

AF:

0.000821

AC:

AN:

58452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.000755

AC:

109

AN:

144354

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

AN XY:

69556

show subpopulations

African (AFR)

AF:

0.000203

AC:

AN:

39490

American (AMR)

AF:

0.000578

AC:

AN:

13836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

4632

South Asian (SAS)

AF:

0.00

AC:

AN:

4524

European-Finnish (FIN)

AF:

0.000594

AC:

AN:

8414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00132

AC:

AN:

66840

Other (OTH)

AF:

0.00

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.00109

Hom.:

Bravo

AF:

0.000737

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000881

AC:

107

ClinVar

Significance: Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 24, 2013

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Nov 27, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28255936, 23861362) -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

CACNB2-related disorder

Benign:1

Nov 06, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;T;.;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D;.;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.046

T;T;T;T;T;T

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

1.0

L;L;.;.;.;.

PhyloP100

7.1

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.5

D;N;N;.;.;N

REVEL

Uncertain

0.46

Sift

Uncertain

0.0010

D;D;D;.;.;D

Sift4G

Benign

0.095

T;T;D;.;.;T

Polyphen

0.98

D;P;D;.;.;D

Vest4

0.93

MVP

0.89

MPC

0.61

ClinPred

0.086

GERP RS

5.9

Varity_R

0.22

gMVP

0.28

Mutation Taster

=67/33

polymorphism

(source)

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

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