rs2357928

chr10-18260712-G-Achr10-18260712-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_201596.3(CACNB2):c.213+109737G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 993,288 control chromosomes in the GnomAD database, including 138,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25503 hom., cov: 31)
  • Exomes 𝑓: 0.52 (113283 hom.)
• Consequence: CACNB2 NM_201596.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-18260712-G-A is Benign according to our data. Variant chr10-18260712-G-A is described in ClinVar as [Benign]. Clinvar id is 1259019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201596.3	c.213+109737G>A		intron_variant		ENST00000324631.13
LOC107984213	XR_001747681.2	n.339+454C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.213+109737G>A		intron_variant		1	NM_201596.3
	ENST00000626127.2	n.27+454C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87015 AN: 151826 Hom.: 25479 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.518 AC: 435445 AN: 841342 Hom.: 113283 Cov.: 34 AF XY: 0.516 AC XY: 200567 AN XY: 388878

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.658

Gnomad4 EAS exome AF: 0.714

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.573 AC: 87084 AN: 151946 Hom.: 25503 Cov.: 31 AF XY: 0.571 AC XY: 42410 AN XY: 74222

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.605

Alfa AF: 0.543 Hom.: 21592

Bravo AF: 0.574

Asia WGS AF: 0.527 AC: 1830 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This variant is associated with the following publications: (PMID: 21156931) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	16
Dann	Benign	0.81

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: rs2357928; hg19: chr10-18549641;