3-54879327-CTTTTT-CTT

Variant names:

• chr3-54879327-CTTT-C
• rs35536476
• NM_018398.3:c.1783-11_1783-9delTTT

Variant summary

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

The NM_018398.3(CACNA2D3):​c.1783-11_1783-9delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,382,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: CACNA2D3 NM_018398.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 1 publications found

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

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.1783-11_1783-9delTTT		intron	N/A	NP_060868.2	Q8IZS8-1
	CACNA2D3-AS1	NR_046666.1		n.534-386_534-384delAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	ENST00000474759.6	TSL:1 MANE Select	c.1783-22_1783-20delTTT		intron	N/A	ENSP00000419101.1	Q8IZS8-1
	CACNA2D3	ENST00000490478.5	TSL:1	c.1501-22_1501-20delTTT		intron	N/A	ENSP00000417279.1	Q8IZS8-2
	CACNA2D3	ENST00000468658.1	TSL:1	n.*1197-22_*1197-20delTTT		intron	N/A	ENSP00000417455.1	F8WAV4

Frequencies

GnomAD3 genomes AF: 0.0000139 AC: 2 AN: 143856 Hom.: 0 Cov.: 0

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: 0.000235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000973 AC: 154 AN: 158340 AF XY: 0.000877

Gnomad AFR exome AF: 0.000649

Gnomad AMR exome AF: 0.00206

Gnomad ASJ exome AF: 0.000453

Gnomad EAS exome AF: 0.00147

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.000674

Gnomad OTH exome AF: 0.000813

GnomAD4 exome AF: 0.000355 AC: 440 AN: 1239038 Hom.: 0 AF XY: 0.000345 AC XY: 214 AN XY: 620398

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

African (AFR) AF: 0.0000363 AC: 1 AN: 27546

American (AMR) AF: 0.00184 AC: 59 AN: 32148

Ashkenazi Jewish (ASJ) AF: 0.000607 AC: 14 AN: 23046

East Asian (EAS) AF: 0.000436 AC: 15 AN: 34398

South Asian (SAS) AF: 0.000718 AC: 52 AN: 72456

European-Finnish (FIN) AF: 0.000528 AC: 23 AN: 43580

Middle Eastern (MID) AF: 0.000412 AC: 2 AN: 4856

European-Non Finnish (NFE) AF: 0.000276 AC: 262 AN: 948986

Other (OTH) AF: 0.000231 AC: 12 AN: 52022

⚠️ 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.

GnomAD4 genome AF: 0.0000139 AC: 2 AN: 143856 Hom.: 0 Cov.: 0 AF XY: 0.0000144 AC XY: 1 AN XY: 69670

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

African (AFR) AF: 0.00 AC: 0 AN: 39036

American (AMR) AF: 0.00 AC: 0 AN: 14562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3378

East Asian (EAS) AF: 0.00 AC: 0 AN: 5008

South Asian (SAS) AF: 0.00 AC: 0 AN: 4526

European-Finnish (FIN) AF: 0.000235 AC: 2 AN: 8500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65690

Other (OTH) AF: 0.00 AC: 0 AN: 1978

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00172 Hom.: 445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs35536476; hg19: chr3-54913354;