Variant 3-54896746-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018398.3(CACNA2D3):c.2247-3A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,662 control chromosomes in the GnomAD database, including 10,957 homozygotes. 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: 𝑓 0.12 ( 1148 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9809 hom. )

Consequence

CACNA2D3
NM_018398.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95

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:

CACNA2D3-AS1 (HGNC:40702): (CACNA2D3 antisense RNA 1)

CACNA2D3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D3	NM_018398.3 linkuse as main transcript	c.2247-3A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000474759.6	NP_060868.2
CACNA2D3-AS1	NR_046666.1 linkuse as main transcript	n.310T>C		non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6 linkuse as main transcript	c.2247-3A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018398.3	ENSP00000419101	P1	Q8IZS8-1
CACNA2D3	ENST00000490478.5 linkuse as main transcript	c.1965-3A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000417279		Q8IZS8-2
CACNA2D3-AS1	ENST00000471265.1 linkuse as main transcript	n.310T>C	non_coding_transcript_exon_variant	2/7	2
CACNA2D3	ENST00000471363.5 linkuse as main transcript	c.*325-3A>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1		ENSP00000418228		Q8IZS8-3

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17544

AN:

152020

Hom.:

1146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0750

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.0112

Gnomad SAS

AF:

0.0527

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0907

AC:

22609

AN:

249272

Hom.:

1252

AF XY:

0.0899

AC XY:

12162

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.0437

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.00851

Gnomad SAS exome

AF:

0.0597

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.0961

GnomAD4 exome

AF:

0.111

AC:

161708

AN:

1461524

Hom.:

9809

Cov.:

AF XY:

0.109

AC XY:

79040

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.0473

Gnomad4 ASJ exome

AF:

0.0324

Gnomad4 EAS exome

AF:

0.0132

Gnomad4 SAS exome

AF:

0.0615

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.115

AC:

17553

AN:

152138

Hom.:

1148

Cov.:

AF XY:

0.113

AC XY:

8398

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0748

Gnomad4 ASJ

AF:

0.0352

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.0529

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.0992

Alfa

AF:

0.108

Hom.:

632

Bravo

AF:

0.111

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.7

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: 3

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over