rs765825655

Variant names:

• chr3-54891420-T-A
• rs765825655
• NM_018398.3:c.2216T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-54891420-T-A
• chr3-54891420-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018398.3(CACNA2D3):​c.2216T>A​(p.Leu739Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNA2D3 NM_018398.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.2216T>A	p.Leu739Gln	missense_variant	Exon 25 of 38	ENST00000474759.6	NP_060868.2
CACNA2D3-AS1	NR_046666.1	n.533+3193A>T		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.2216T>A	p.Leu739Gln	missense_variant	Exon 25 of 38	1	NM_018398.3	ENSP00000419101.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T;T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.91	.;D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M;M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.78	P;P;P;.
Vest4		0.97
MutPred		0.54		Loss of stability (P = 0.0019);Loss of stability (P = 0.0019);Loss of stability (P = 0.0019);.;
MVP		0.62
MPC		0.96
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.76

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

Other links and lift over

dbSNP: rs765825655; hg19: chr3-54925447;