chr10-18514275-A-G

Variant names:

• chr10-18514275-A-G
• NM_201596.3:c.710A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201596.3(CACNB2):​c.710A>G​(p.Asn237Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. 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. N237D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CACNB2 NM_201596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

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:58168):

LOC124902386 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06503126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3	c.710A>G	p.Asn237Ser	missense_variant	Exon 7 of 14	ENST00000324631.13	NP_963890.2
CACNB2	NM_201590.3	c.548A>G	p.Asn183Ser	missense_variant	Exon 6 of 13	ENST00000377329.10	NP_963884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13	c.710A>G	p.Asn237Ser	missense_variant	Exon 7 of 14	1	NM_201596.3	ENSP00000320025.8
CACNB2	ENST00000377329.10	c.548A>G	p.Asn183Ser	missense_variant	Exon 6 of 13	1	NM_201590.3	ENSP00000366546.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.046	T;.;.;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.065	T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.0	N;.;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.19	N;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.45	T;T;T;T;T
Sift4G	Benign	0.77	T;T;T;T;T
Polyphen		0.0	B;B;.;B;.
Vest4		0.18
MutPred		0.33		Gain of glycosylation at N237 (P = 0.0071);.;.;.;.;
MVP		0.78
MPC		0.16
ClinPred		0.32	T
GERP RS		4.8
Varity_R		0.056
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-18803204;