10-18381088-G-A

Variant names:

• chr10-18381088-G-A
• rs10828616
• NM_201596.3:c.214-20836G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201596.3(CACNB2):​c.214-20836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,292 control chromosomes in the GnomAD database, including 5,233 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 0.25 (5233 hom., cov: 28)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 2 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.214-20836G>A		intron_variant	Intron 2 of 13	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.52-20836G>A		intron_variant	Intron 1 of 12	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.214-20836G>A		intron_variant	Intron 2 of 13	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.52-20836G>A		intron_variant	Intron 1 of 12	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37712 AN: 151174 Hom.: 5230 Cov.: 28

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.249 AC: 37738 AN: 151292 Hom.: 5233 Cov.: 28 AF XY: 0.252 AC XY: 18631 AN XY: 73830

African (AFR) AF: 0.216 AC: 8918 AN: 41232

American (AMR) AF: 0.227 AC: 3439 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1313 AN: 3464

East Asian (EAS) AF: 0.660 AC: 3343 AN: 5064

South Asian (SAS) AF: 0.283 AC: 1348 AN: 4764

European-Finnish (FIN) AF: 0.251 AC: 2625 AN: 10470

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15926 AN: 67872

Other (OTH) AF: 0.285 AC: 598 AN: 2100

Alfa AF: 0.245 Hom.: 18558

Bravo AF: 0.252

Asia WGS AF: 0.470 AC: 1633 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	0.61
DANN	Benign	0.22
PhyloP100		-0.014
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10828616; hg19: chr10-18670017;