10-18150970-C-G

Variant names:

• chr10-18150970-C-G
• rs760538597
• NM_201596.3:c.208C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_201596.3(CACNB2):​c.208C>G​(p.Arg70Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,419,618 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R70C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CACNB2 NM_201596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.208C>G	p.Arg70Gly	missense_variant	Exon 2 of 14	ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.208C>G	p.Arg70Gly	missense_variant	Exon 2 of 14	1	NM_201596.3	ENSP00000320025.8

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251054 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135700

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1419618 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 706912

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;.;T;.;.;.
Eigen	Benign	-0.024
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;T;T;.;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Benign	1.0	L;L;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.8	D;D;D;.;.;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D;D;D;.;.;D
Sift4G	Uncertain	0.060	T;T;D;.;.;T
Polyphen		0.40	B;B;P;.;.;B
Vest4		0.92
MutPred		0.27		Loss of stability (P = 0.0481);Loss of stability (P = 0.0481);Loss of stability (P = 0.0481);.;.;.;
MVP		0.89
MPC		0.34
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.45
gMVP		0.41

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: rs760538597; hg19: chr10-18439899;