10-18539262-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_201596.3(CACNB2):c.1521C>T(p.Ser507Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00769 in 1,613,944 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0079 ( 57 hom. )

Consequence

CACNB2
NM_201596.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.383

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 links:

ENSG00000240291 (HGNC:58168):

ENSG00000240291 links:

LOC124902386 (HGNC:):

LOC124902386 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.568183).

BP6

Variant 10-18539262-C-T is Benign according to our data. Variant chr10-18539262-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 242261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-18539262-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.383 with no splicing effect.

BS2

High AC in GnomAd4 at 829 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.1521C>T	p.Ser507Ser	synonymous_variant	Exon 14 of 14	ENST00000324631.13	NP_963890.2	Q08289-1
CACNB2	NM_201590.3 link	c.1359C>T	p.Ser453Ser	synonymous_variant	Exon 13 of 13	ENST00000377329.10	NP_963884.2	Q08289-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 link	c.1521C>T	p.Ser507Ser	synonymous_variant	Exon 14 of 14	1	NM_201596.3	ENSP00000320025.8		Q08289-1
CACNB2	ENST00000377329.10 link	c.1359C>T	p.Ser453Ser	synonymous_variant	Exon 13 of 13	1	NM_201590.3	ENSP00000366546.4		Q08289-3

Frequencies

GnomAD3 genomes

AF:

0.00546

AC:

830

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00336

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00460

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00841

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00475

AC:

1194

AN:

251322

Hom.:

AF XY:

0.00470

AC XY:

638

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.000816

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00762

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00792

AC:

11575

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00781

AC XY:

5680

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00311

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00944

Gnomad4 OTH exome

AF:

0.00695

GnomAD4 genome

AF:

0.00545

AC:

829

AN:

152098

Hom.:

Cov.:

AF XY:

0.00496

AC XY:

369

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00333

Gnomad4 AMR

AF:

0.00459

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00841

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00408

Hom.:

Bravo

AF:

0.00575

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.00826

AC:

ExAC

AF:

0.00446

AC:

542

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CACNB2: BP4, BP7, BS2; ENSG00000240291: BS2 -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Brugada syndrome 4

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 05, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Nov 27, 2015

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.5

DANN

Benign

0.79

FATHMM_MKL

Benign

0.0089

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over