rs142899184

chr10-18515022-G-Achr10-18515022-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000352115.10(CACNB2):c.713G>A(p.Gly238Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,613,692 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (4 hom.)
• Consequence: CACNB2 ENST00000352115.10 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.74

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]

LOC124902386 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007593423).
• BP6: Variant 10-18515022-G-A is Benign according to our data. Variant chr10-18515022-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 191568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-18515022-G-A is described in Lovd as [Benign].
• BS2: High AC in GnomAd at 417 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNB2	NM_201590.3	c.642+653G>A		intron_variant		ENST00000377329.10
CACNB2	NM_201596.3	c.804+653G>A		intron_variant		ENST00000324631.13
LOC124902386	XR_007062076.1	n.3892C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNB2	ENST00000324631.13	c.804+653G>A		intron_variant		1	NM_201596.3
CACNB2	ENST00000377329.10	c.642+653G>A		intron_variant		1	NM_201590.3
	ENST00000425669.1	n.483-1362C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152136 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00958

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

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: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000753 AC: 189 AN: 251154 Hom.: 3 AF XY: 0.000354 AC XY: 48 AN XY: 135720

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000294 AC: 430 AN: 1461438 Hom.: 4 Cov.: 30 AF XY: 0.000238 AC XY: 173 AN XY: 727060

Gnomad4 AFR exome AF: 0.00986

Gnomad4 AMR exome AF: 0.000470

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: 0.0000279

Gnomad4 OTH exome AF: 0.000762

GnomAD4 genome AF: 0.00274 AC: 417 AN: 152254 Hom.: 3 Cov.: 33 AF XY: 0.00249 AC XY: 185 AN XY: 74434

Gnomad4 AFR AF: 0.00955

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000721 Hom.: 0

Bravo AF: 0.00331

ESP6500AA AF: 0.0116 AC: 51

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000906 AC: 110

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

- -

Brugada syndrome 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	22
Dann	Benign	0.83
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.53	T;T;T
MetaRNN	Benign	0.0076	T;T;T
MetaSVM	Benign	-0.69	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;N;N
PROVEAN	Benign	-0.030	N;.;.
REVEL	Benign	0.27
Sift	Benign	0.62	T;.;.
Sift4G	Benign	0.36	T;.;T
Polyphen		0.0	B;.;.
Vest4		0.15
MVP		0.69
ClinPred		0.011	T
GERP RS		4.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs142899184; hg19: chr10-18803951;