Genetic Variant CACNB2:c.213+65619T>A (chr10-18216594-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_201596.3(CACNB2):c.213+65619T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,806 control chromosomes in the GnomAD database, including 35,361 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35361 hom., cov: 32)

Consequence

CACNB2
NM_201596.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

Publications

1 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:

ENSG00000235020 (HGNC:58169):

ENSG00000235020 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.213+65619T>A		intron_variant	Intron 2 of 13	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.213+65619T>A		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8		Q08289-1

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101127

AN:

151690

Hom.:

35356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.691

Gnomad FIN

AF:

0.754

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.787

Gnomad OTH

AF:

0.690

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.666

AC:

101167

AN:

151806

Hom.:

35361

Cov.:

AF XY:

0.668

AC XY:

49541

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.454

AC:

18783

AN:

41388

American (AMR)

AF:

0.728

AC:

11101

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

2376

AN:

3468

East Asian (EAS)

AF:

0.372

AC:

1915

AN:

5148

South Asian (SAS)

AF:

0.692

AC:

3328

AN:

4812

European-Finnish (FIN)

AF:

0.754

AC:

7945

AN:

10540

Middle Eastern (MID)

AF:

0.728

AC:

211

AN:

290

European-Non Finnish (NFE)

AF:

0.787

AC:

53433

AN:

67898

Other (OTH)

AF:

0.691

AC:

1459

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1601

3202

4803

6404

8005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.652

Hom.:

2229

Bravo

AF:

0.651

Asia WGS

AF:

0.577

AC:

2009

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.1

(source)

DANN

Benign

0.80

PhyloP100

-0.031

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over