Variant chr10-18150971-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_201596.3(CACNB2):c.209G>T(p.Arg70Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000574 in 1,568,728 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

CACNB2
NM_201596.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.14

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:

CACNB2 (HGNC:):

CACNB2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3 linkuse as main transcript	c.209G>T	p.Arg70Leu	missense_variant	2/14	ENST00000324631.13	NP_963890.2	Q08289-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 linkuse as main transcript	c.209G>T	p.Arg70Leu	missense_variant	2/14	1	NM_201596.3	ENSP00000320025.8		Q08289-1

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

144244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000491

AC:

AN:

1424484

Hom.:

Cov.:

AF XY:

0.00000564

AC XY:

AN XY:

709548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000646

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000139

AC:

AN:

144244

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

69444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000299

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000289

AC:

AN:

3472

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.;T;.;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D;D;.;D;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.59

D;D;D;D;D;D

MetaSVM

Uncertain

-0.00050

MutationAssessor

Benign

1.0

L;L;.;.;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.5

D;D;D;.;.;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

D;D;D;.;.;D

Sift4G

Benign

0.10

T;T;D;.;.;T

Polyphen

0.77

P;B;P;.;.;P

Vest4

0.88

MutPred

0.32

Gain of glycosylation at S73 (P = 0.0806);Gain of glycosylation at S73 (P = 0.0806);Gain of glycosylation at S73 (P = 0.0806);.;.;.;

MVP

0.88

MPC

0.30

ClinPred

0.84

GERP RS

5.9

Varity_R

0.33

gMVP

0.36

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over