rs2239801

Variant names:

• chr3-50364878-C-G
• rs2239801
• NM_006030.4:c.3291+10G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-50364878-C-G
• chr3-50364878-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.11

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]

ENSG00000272104 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
CACNA2D2	NM_006030.4	c.3291+10G>C		intron_variant	Intron 37 of 37	ENST00000424201.7	NP_006021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D2	ENST00000424201.7	c.3291+10G>C		intron_variant	Intron 37 of 37	1	NM_006030.4	ENSP00000390329.2
CACNA2D2	ENST00000423994.6	c.3321+10G>C		intron_variant	Intron 38 of 38	5		ENSP00000407393.2
CACNA2D2	ENST00000266039.7	c.3297+10G>C		intron_variant	Intron 37 of 37	1		ENSP00000266039.3
CACNA2D2	ENST00000360963.7	c.3090+10G>C		intron_variant	Intron 37 of 37	1		ENSP00000354228.3
ENSG00000272104	ENST00000606589.1	c.128-1419C>G		intron_variant	Intron 2 of 3	3		ENSP00000476225.1

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12452 AN: 152152 Hom.: 618 Cov.: 32

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

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.: 35 AF XY: 0.108 AC XY: 78687 AN XY: 726834

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.: 32 AF XY: 0.0822 AC XY: 6118 AN XY: 74440

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

Submissions by phenotype

not provided Benign:3

Nov 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	-0.80
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

Other links and lift over

dbSNP: rs2239801; hg19: chr3-50402309; COSMIC: COSV56561717; COSMIC: COSV56561717;