Genetic Variant CACNA2D3:c.1783-10_1783-9dupTT (chr3-54879327-C-CTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018398.3(CACNA2D3):c.1783-10_1783-9dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

CACNA2D3
NM_018398.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.06

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:

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

CACNA2D3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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.1783-10_1783-9dupTT		splice_region intron	N/A	NP_060868.2	Q8IZS8-1
	CACNA2D3-AS1	NR_046666.1		n.534-385_534-384dupAA		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CACNA2D3	ENST00000474759.6	TSL:1 MANE Select	c.1783-23_1783-22insTT	intron	N/A	ENSP00000419101.1	Q8IZS8-1
CACNA2D3	ENST00000490478.5	TSL:1	c.1501-23_1501-22insTT	intron	N/A	ENSP00000417279.1	Q8IZS8-2
CACNA2D3	ENST00000468658.1	TSL:1	n.1197-23_1197-22insTT	intron	N/A	ENSP00000417455.1	F8WAV4

Frequencies

GnomAD3 genomes

AF:

0.00000695

AC:

AN:

143854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00338

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000505

AC:

AN:

158340

AF XY:

0.000427

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.000302

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.000184

Gnomad FIN exome

AF:

0.000395

Gnomad NFE exome

AF:

0.000542

Gnomad OTH exome

AF:

0.000271

GnomAD4 exome

AF:

0.000236

AC:

293

AN:

1241754

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

141

AN XY:

621810

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00116

AC:

AN:

27576

American (AMR)

AF:

0.000154

AC:

AN:

32500

Ashkenazi Jewish (ASJ)

AF:

0.000130

AC:

AN:

23096

East Asian (EAS)

AF:

0.0000575

AC:

AN:

34756

South Asian (SAS)

AF:

0.000220

AC:

AN:

72822

European-Finnish (FIN)

AF:

0.0000457

AC:

AN:

43744

Middle Eastern (MID)

AF:

0.000616

AC:

AN:

4872

European-Non Finnish (NFE)

AF:

0.000234

AC:

222

AN:

950272

Other (OTH)

AF:

0.000154

AC:

AN:

52116

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

122

162

203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000695

AC:

AN:

143892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39108

American (AMR)

AF:

0.00

AC:

AN:

14576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3378

East Asian (EAS)

AF:

0.00

AC:

AN:

4996

South Asian (SAS)

AF:

0.00

AC:

AN:

4502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8500

Middle Eastern (MID)

AF:

0.00357

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65680

Other (OTH)

AF:

0.00

AC:

AN:

1990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over