chr10-18539262-C-T

Position:

chr10-18539262-C-T

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:):

ENSG00000240291 links:

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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/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3 linkuse as main transcript	c.1521C>T	p.Ser507Ser	synonymous_variant	14/14	ENST00000324631.13	NP_963890.2	Q08289-1
CACNB2	NM_201590.3 linkuse as main transcript	c.1359C>T	p.Ser453Ser	synonymous_variant	13/13	ENST00000377329.10	NP_963884.2	Q08289-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 linkuse as main transcript	c.1521C>T	p.Ser507Ser	synonymous_variant	14/14	1	NM_201596.3	ENSP00000320025.8		Q08289-1
CACNB2	ENST00000377329.10 linkuse as main transcript	c.1359C>T	p.Ser453Ser	synonymous_variant	13/13	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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	CACNB2: BP4, BP7, BS2; ENSG00000240291: BS2 -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Brugada syndrome 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 05, 2021	- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2015

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