Genetic Variant CACNA2D3:p.Arg32Cys (chr3-54122807-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018398.3(CACNA2D3):c.94C>T(p.Arg32Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R32S) 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: 3.28

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29784152).

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.94C>T	p.Arg32Cys	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.94C>T	p.Arg32Cys	missense	Exon 1 of 38	ENSP00000419101.1	Q8IZS8-1
CACNA2D3	ENST00000958523.1		c.94C>T	p.Arg32Cys	missense	Exon 1 of 37	ENSP00000628582.1
CACNA2D3	ENST00000958525.1		c.94C>T	p.Arg32Cys	missense	Exon 1 of 36	ENSP00000628584.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

7030

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1080408

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

510280

African (AFR)

AF:

0.00

AC:

AN:

22594

American (AMR)

AF:

0.00

AC:

AN:

8110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13956

East Asian (EAS)

AF:

0.00

AC:

AN:

26002

South Asian (SAS)

AF:

0.00

AC:

AN:

19434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2884

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

914702

Other (OTH)

AF:

0.00

AC:

AN:

43024

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.73

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

PhyloP100

3.3

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.9

REVEL

Benign

0.083

Sift

Benign

0.095

Sift4G

Benign

0.089

Polyphen

1.0

Vest4

0.12

MutPred

0.41

Loss of solvent accessibility (P = 0.0299)

MVP

0.068

MPC

0.39

ClinPred

0.77

GERP RS

3.7

PromoterAI

0.067

Neutral

(source)

Varity_R

0.20

gMVP

0.30

Mutation Taster

=83/17

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

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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