chr10-18140740-G-T

Variant names:

• chr10-18140740-G-T
• rs780368829
• NM_201596.3:c.4G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_201596.3(CACNB2):​c.4G>T​(p.Val2Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,441,288 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CACNB2 NM_201596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.4G>T	p.Val2Phe	missense_variant	Exon 1 of 14	ENST00000324631.13	NP_963890.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.4G>T	p.Val2Phe	missense_variant	Exon 1 of 14	1	NM_201596.3	ENSP00000320025.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000962 AC: 2 AN: 207958 Hom.: 0 AF XY: 0.0000176 AC XY: 2 AN XY: 113538

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: 0.0000220

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000416 AC: 6 AN: 1441288 Hom.: 0 Cov.: 32 AF XY: 0.00000560 AC XY: 4 AN XY: 714826

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: 0.00000544

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000834 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	26
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.26	T;T;T
M_CAP	Pathogenic	0.83	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.1	N;N;N
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.82	P;B;P
Vest4		0.73
MutPred		0.20		Loss of catalytic residue at V2 (P = 0.0544);Loss of catalytic residue at V2 (P = 0.0544);Loss of catalytic residue at V2 (P = 0.0544);
MVP		0.88
MPC		0.90
ClinPred		0.52	D
GERP RS		2.0
Varity_R		0.35
gMVP		0.43

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: rs780368829; hg19: chr10-18429669;