10-18539442-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_201596.3(CACNB2):c.1701C>T(p.Tyr567Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,613,638 control chromosomes in the GnomAD database, including 29,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3194 hom., cov: 30)

Exomes 𝑓: 0.18 ( 26070 hom. )

Consequence

CACNB2
NM_201596.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.61

Publications

21 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:

ENSG00000240291 (HGNC:58168):

ENSG00000240291 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-18539442-C-T is Benign according to our data. Variant chr10-18539442-C-T is described in ClinVar as Benign. ClinVar VariationId is 263261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.1701C>T	p.Tyr567Tyr	synonymous_variant	Exon 14 of 14	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3 link	c.1539C>T	p.Tyr513Tyr	synonymous_variant	Exon 13 of 13	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 link	c.1701C>T	p.Tyr567Tyr	synonymous_variant	Exon 14 of 14	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10 link	c.1539C>T	p.Tyr513Tyr	synonymous_variant	Exon 13 of 13	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29759

AN:

151762

Hom.:

3193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.189

GnomAD2 exomes

AF:

0.219

AC:

55096

AN:

251094

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.180

AC:

263797

AN:

1461758

Hom.:

26070

Cov.:

AF XY:

0.183

AC XY:

133312

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.193

AC:

6470

AN:

33480

American (AMR)

AF:

0.375

AC:

16746

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

4197

AN:

26136

East Asian (EAS)

AF:

0.262

AC:

10399

AN:

39688

South Asian (SAS)

AF:

0.290

AC:

25052

AN:

86254

European-Finnish (FIN)

AF:

0.190

AC:

10170

AN:

53418

Middle Eastern (MID)

AF:

0.122

AC:

702

AN:

5768

European-Non Finnish (NFE)

AF:

0.161

AC:

179449

AN:

1111924

Other (OTH)

AF:

0.176

AC:

10612

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

14278

28557

42835

57114

71392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6640

13280

19920

26560

33200

<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:

0.196

AC:

29780

AN:

151880

Hom.:

3194

Cov.:

AF XY:

0.202

AC XY:

15003

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.201

AC:

8331

AN:

41428

American (AMR)

AF:

0.284

AC:

4333

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

528

AN:

3466

East Asian (EAS)

AF:

0.230

AC:

1180

AN:

5130

South Asian (SAS)

AF:

0.299

AC:

1432

AN:

4784

European-Finnish (FIN)

AF:

0.196

AC:

2072

AN:

10576

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11330

AN:

67948

Other (OTH)

AF:

0.187

AC:

393

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1154

2308

3461

4615

5769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.173

Hom.:

5193

Bravo

AF:

0.199

Asia WGS

AF:

0.304

AC:

1059

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Brugada syndrome 4

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cardiovascular phenotype

Benign:1

Jun 18, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.38

(source)

DANN

Benign

0.83

PhyloP100

-2.6

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over