rs2482109

Positions:

• chr10-18236241-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201596.3(CACNB2):​c.213+85266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,136 control chromosomes in the GnomAD database, including 55,756 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 0.85 (55756 hom., cov: 32)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201596.3	c.213+85266G>A		intron_variant		ENST00000324631.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.213+85266G>A		intron_variant		1	NM_201596.3
	ENST00000626127.2	n.27+24925C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129705 AN: 152018 Hom.: 55700 Cov.: 32

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.853 AC: 129821 AN: 152136 Hom.: 55756 Cov.: 32 AF XY: 0.851 AC XY: 63271 AN XY: 74380

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.833

Alfa AF: 0.845 Hom.: 9278

Bravo AF: 0.861

Asia WGS AF: 0.758 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs2482109; hg19: chr10-18525170;