Genetic Variant CACNA2D3:p.Arg12Leu (chr3-54122748-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018398.3(CACNA2D3):c.35G>T(p.Arg12Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CACNA2D3
NM_018398.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.75

Publications

0 publications found

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:

ENSG00000286353 (HGNC:):

ENSG00000286353 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12267056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018398.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	NM_018398.3	MANE Select	c.35G>T	p.Arg12Leu	missense	Exon 1 of 38	NP_060868.2	Q8IZS8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNA2D3	ENST00000474759.6	TSL:1 MANE Select	c.35G>T	p.Arg12Leu	missense	Exon 1 of 38	ENSP00000419101.1	Q8IZS8-1
CACNA2D3	ENST00000958523.1		c.35G>T	p.Arg12Leu	missense	Exon 1 of 37	ENSP00000628582.1
CACNA2D3	ENST00000958525.1		c.35G>T	p.Arg12Leu	missense	Exon 1 of 36	ENSP00000628584.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1066146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

503368

African (AFR)

AF:

0.00

AC:

AN:

22260

American (AMR)

AF:

0.00

AC:

AN:

7814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13512

East Asian (EAS)

AF:

0.00

AC:

AN:

25204

South Asian (SAS)

AF:

0.00

AC:

AN:

19338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2824

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

908866

Other (OTH)

AF:

0.00

AC:

AN:

42348

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.85

PhyloP100

3.8

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.41

REVEL

Benign

0.064

Sift

Benign

0.99

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.27

MutPred

0.47

Loss of MoRF binding (P = 0.0016)

MVP

0.043

MPC

0.33

ClinPred

0.72

GERP RS

4.2

PromoterAI

0.028

Neutral

(source)

Varity_R

0.16

gMVP

0.39

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over