Genetic Variant NM_201596.3:c.1539T>A (chr10-18539280-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_201596.3(CACNB2):c.1539T>A(p.Ala513Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CACNB2
NM_201596.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.120

Variant links:

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 links:

ENSG00000240291 (HGNC:58168):

ENSG00000240291 links:

LOC124902386 (HGNC:):

LOC124902386 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNB2	NM_201596.3 link	c.1539T>A	p.Ala513Ala	synonymous_variant	Exon 14 of 14	ENST00000324631.13	NP_963890.2	Q08289-1
CACNB2	NM_201590.3 link	c.1377T>A	p.Ala459Ala	synonymous_variant	Exon 13 of 13	ENST00000377329.10	NP_963884.2	Q08289-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB2	ENST00000324631.13 link	c.1539T>A	p.Ala513Ala	synonymous_variant	Exon 14 of 14	1	NM_201596.3	ENSP00000320025.8		Q08289-1
CACNB2	ENST00000377329.10 link	c.1377T>A	p.Ala459Ala	synonymous_variant	Exon 13 of 13	1	NM_201590.3	ENSP00000366546.4		Q08289-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.1

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over