Variant 3-54562940-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018398.3(CACNA2D3):c.676+9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,611,664 control chromosomes in the GnomAD database, including 4,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 1555 hom., cov: 32)

Exomes 𝑓: 0.025 ( 2534 hom. )

Consequence

CACNA2D3
NM_018398.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.31

Variant links:

Genes affected

CACNA2D3 (HGNC:15460): (calcium voltage-gated channel auxiliary subunit alpha2delta 3) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

CACNA2D3 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=-0.79).

BP6

Variant 3-54562940-A-C is Benign according to our data. Variant chr3-54562940-A-C is described in ClinVar as [Benign]. Clinvar id is 1269269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D3	NM_018398.3 link	c.676+9A>C		intron_variant		ENST00000474759.6	NP_060868.2	Q8IZS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6 link	c.676+9A>C		intron_variant		1	NM_018398.3	ENSP00000419101.1		Q8IZS8-1

Frequencies

GnomAD3 genomes

AF:

0.0928

AC:

14117

AN:

152110

Hom.:

1555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0815

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.0363

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00878

Gnomad OTH

AF:

0.0705

GnomAD3 exomes

AF:

0.0563

AC:

13989

AN:

248376

Hom.:

1184

AF XY:

0.0477

AC XY:

6431

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.00697

Gnomad EAS exome

AF:

0.215

Gnomad SAS exome

AF:

0.0318

Gnomad FIN exome

AF:

0.0167

Gnomad NFE exome

AF:

0.00762

Gnomad OTH exome

AF:

0.0306

GnomAD4 exome

AF:

0.0250

AC:

36505

AN:

1459436

Hom.:

2534

Cov.:

AF XY:

0.0240

AC XY:

17402

AN XY:

726044

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.00621

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.0322

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.00793

Gnomad4 OTH exome

AF:

0.0389

GnomAD4 genome

AF:

0.0928

AC:

14124

AN:

152228

Hom.:

1555

Cov.:

AF XY:

0.0927

AC XY:

6904

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.0812

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.0361

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.00878

Gnomad4 OTH

AF:

0.0712

Alfa

AF:

0.0724

Hom.:

400

Bravo

AF:

0.108

Asia WGS

AF:

0.111

AC:

388

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 30, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.2

DANN

Benign

0.68

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