10-18260712-G-A

Variant names:

• chr10-18260712-G-A
• rs2357928
• NM_201596.3:c.213+109737G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.79
• Publications: 18 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• cardiogenetic disease

  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

CACNB2-AS2 (HGNC:58169):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1259019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201596.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	NM_201596.3	MANE Select	c.213+109737G>A		intron	N/A	NP_963890.2	Q08289-1
	CACNB2	NM_201597.3		c.213+109737G>A		intron	N/A	NP_963891.1	Q08289-8
	CACNB2	NM_201571.4		c.129+109737G>A		intron	N/A	NP_963865.2	Q08289-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	ENST00000324631.13	TSL:1 MANE Select	c.213+109737G>A		intron	N/A	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000352115.10	TSL:1	c.213+109737G>A		intron	N/A	ENSP00000344474.6	Q08289-8
	CACNB2	ENST00000282343.13	TSL:1	c.129+109737G>A		intron	N/A	ENSP00000282343.8	Q08289-4

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

African (AFR) AF: 0.685 AC: 10923 AN: 15944

American (AMR) AF: 0.460 AC: 1265 AN: 2752

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 3440 AN: 5228

East Asian (EAS) AF: 0.714 AC: 2873 AN: 4024

South Asian (SAS) AF: 0.417 AC: 7186 AN: 17214

European-Finnish (FIN) AF: 0.582 AC: 228 AN: 392

Middle Eastern (MID) AF: 0.594 AC: 974 AN: 1640

European-Non Finnish (NFE) AF: 0.514 AC: 393773 AN: 766474

Other (OTH) AF: 0.534 AC: 14783 AN: 27674

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

African (AFR) AF: 0.671 AC: 27794 AN: 41444

American (AMR) AF: 0.494 AC: 7540 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2275 AN: 3472

East Asian (EAS) AF: 0.703 AC: 3614 AN: 5140

South Asian (SAS) AF: 0.421 AC: 2024 AN: 4808

European-Finnish (FIN) AF: 0.574 AC: 6051 AN: 10550

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36044 AN: 67944

Other (OTH) AF: 0.605 AC: 1276 AN: 2110

Alfa AF: 0.547 Hom.: 63505

Bravo AF: 0.574

Asia WGS AF: 0.527 AC: 1830 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		1.8
PromoterAI		-0.037	Neutral
Mutation Taster		=99/1	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: rs2357928; hg19: chr10-18549641;