NM_201596.3:c.79G>C

Variant names:

• chr10-18140815-G-C
• rs2030299512
• NM_201596.3:c.79G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201596.3(CACNB2):​c.79G>C​(p.Glu27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNB2 NM_201596.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 0 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30982983).

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.79G>C	p.Glu27Gln	missense	Exon 1 of 14	NP_963890.2	Q08289-1
	CACNB2	NM_201597.3		c.79G>C	p.Glu27Gln	missense	Exon 1 of 14	NP_963891.1	Q08289-8
	CACNB2	NM_201593.3		c.79G>C	p.Glu27Gln	missense	Exon 1 of 14	NP_963887.2	Q08289-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNB2	ENST00000324631.13	TSL:1 MANE Select	c.79G>C	p.Glu27Gln	missense	Exon 1 of 14	ENSP00000320025.8	Q08289-1
	CACNB2	ENST00000352115.10	TSL:1	c.79G>C	p.Glu27Gln	missense	Exon 1 of 14	ENSP00000344474.6	Q08289-8
	CACNB2	ENST00000377328.5	TSL:1	c.79G>C	p.Glu27Gln	missense	Exon 1 of 7	ENSP00000366545.1	A6PVM6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.43	T
Polyphen		0.089	B
Vest4		0.29
MutPred		0.23		Gain of helix (P = 0.132)
MVP		0.85
MPC		0.20
ClinPred		0.24	T
GERP RS		3.0
PromoterAI		-0.013	Neutral
Varity_R		0.18
gMVP		0.18
Mutation Taster		=95/5	polymorphism

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: rs2030299512; hg19: chr10-18429744;