Genetic Variant CACNA2D2:c.2045+10G>A (chr3-50370310-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_006030.4(CACNA2D2):c.2045+10G>A variant causes a intron change. The variant allele was found at a frequency of 0.0000444 in 1,575,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 1 hom. )

Consequence

CACNA2D2
NM_006030.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

CACNA2D2 (HGNC:1400): (calcium voltage-gated channel auxiliary subunit alpha2delta 2) Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

CACNA2D2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.17).

BP6

Variant 3-50370310-C-T is Benign according to our data. Variant chr3-50370310-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461305.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D2	NM_006030.4 link	c.2045+10G>A		intron_variant	Intron 23 of 37	ENST00000424201.7	NP_006021.2	Q9NY47-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA2D2	ENST00000424201.7 link	c.2045+10G>A	intron_variant	Intron 23 of 37	1	NM_006030.4	ENSP00000390329.2	Q9NY47-2
CACNA2D2	ENST00000423994.6 link	c.2066+10G>A	intron_variant	Intron 24 of 38	5		ENSP00000407393.2	C9JVC9
CACNA2D2	ENST00000266039.7 link	c.2045+10G>A	intron_variant	Intron 23 of 37	1		ENSP00000266039.3	Q9NY47-3
CACNA2D2	ENST00000360963.7 link	c.1838+10G>A	intron_variant	Intron 23 of 37	1		ENSP00000354228.3	Q9NY47-4

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000461

AC:

AN:

195324

Hom.:

AF XY:

0.0000575

AC XY:

AN XY:

104430

show subpopulations

Gnomad AFR exome

AF:

0.0000896

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000241

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000236

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000449

AC:

AN:

1423842

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

704730

show subpopulations

Gnomad4 AFR exome

AF:

0.0000616

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000134

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000348

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151772

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Jul 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over