chr10-18539639-G-C

Position:

• chr10-18539639-G-C

Variant summary

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

The NM_201596.3(CACNB2):​c.1898G>C​(p.Arg633Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CACNB2 NM_201596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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]

ENSG00000240291 (HGNC:):

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/exons	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.1898G>C	p.Arg633Pro	missense_variant	14/14	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.1736G>C	p.Arg579Pro	missense_variant	13/13	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.1898G>C	p.Arg633Pro	missense_variant	14/14	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.1736G>C	p.Arg579Pro	missense_variant	13/13	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;T;.;.;.;T;T;.;.;.;T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;.;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Uncertain	2.1	M;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.0	N;N;N;.;.;N;.;.;N;N;N;.;N;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0040	D;D;D;.;.;D;.;.;D;D;D;.;D;.
Sift4G	Uncertain	0.0090	D;D;D;.;.;D;D;D;D;D;D;D;D;.
Polyphen		0.97	D;D;D;.;.;P;.;.;.;P;P;.;.;.
Vest4		0.33
MutPred		0.43		Loss of MoRF binding (P = 3e-04);.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP		0.91
MPC		0.68
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.18

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: rs780045364; hg19: chr10-18828568;