rs2239801

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006030.4(CACNA2D2):c.3291+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,613,314 control chromosomes in the GnomAD database, including 9,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 621 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8810 hom. )

Consequence

CACNA2D2
NM_006030.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.11

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:

ENSG00000272104 (HGNC:):

ENSG00000272104 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-50364878-C-G is Benign according to our data. Variant chr3-50364878-C-G is described in ClinVar as [Benign]. Clinvar id is 585338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D2	NM_006030.4 linkuse as main transcript	c.3291+10G>C		intron_variant		ENST00000424201.7	NP_006021.2	Q9NY47-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CACNA2D2	ENST00000424201.7 linkuse as main transcript	c.3291+10G>C	intron_variant	1	NM_006030.4	ENSP00000390329.2	Q9NY47-2
CACNA2D2	ENST00000423994.6 linkuse as main transcript	c.3321+10G>C	intron_variant	5		ENSP00000407393.2	C9JVC9
CACNA2D2	ENST00000266039.7 linkuse as main transcript	c.3297+10G>C	intron_variant	1		ENSP00000266039.3	Q9NY47-3
CACNA2D2	ENST00000360963.7 linkuse as main transcript	c.3090+10G>C	intron_variant	1		ENSP00000354228.3	Q9NY47-4
ENSG00000272104	ENST00000606589.1 linkuse as main transcript	c.128-1419C>G	intron_variant	3		ENSP00000476225.1	U3KQU4

Frequencies

GnomAD3 genomes

AF:

0.0818

AC:

12452

AN:

152152

Hom.:

618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.0742

Gnomad ASJ

AF:

0.0735

Gnomad EAS

AF:

0.0572

Gnomad SAS

AF:

0.0957

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0875

GnomAD3 exomes

AF:

0.0963

AC:

23966

AN:

248880

Hom.:

1283

AF XY:

0.0989

AC XY:

13360

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.0721

Gnomad ASJ exome

AF:

0.0749

Gnomad EAS exome

AF:

0.0567

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.108

AC:

157503

AN:

1461044

Hom.:

8810

Cov.:

AF XY:

0.108

AC XY:

78687

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.0221

Gnomad4 AMR exome

AF:

0.0734

Gnomad4 ASJ exome

AF:

0.0758

Gnomad4 EAS exome

AF:

0.0792

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0818

AC:

12456

AN:

152270

Hom.:

621

Cov.:

AF XY:

0.0822

AC XY:

6118

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.0740

Gnomad4 ASJ

AF:

0.0735

Gnomad4 EAS

AF:

0.0570

Gnomad4 SAS

AF:

0.0960

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0903

Alfa

AF:

0.0942

Hom.:

139

Bravo

AF:

0.0746

Asia WGS

AF:

0.0960

AC:

335

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 19. Only high quality variants are reported. -

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.4

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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