3-54879327-CTTTTT-CT

Variant names:

• chr3-54879327-CTTTT-C
• rs35536476
• NM_018398.3:c.1783-12_1783-9delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018398.3(CACNA2D3):​c.1783-12_1783-9delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,243,938 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: not found (cov: 0)
  • Exomes 𝑓: 0.000018 (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1783-12_1783-9delTTTT		intron	N/A	NP_060868.2	Q8IZS8-1
	CACNA2D3-AS1	NR_046666.1		n.534-387_534-384delAAAA		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_1783-19delTTTT		intron	N/A	ENSP00000419101.1	Q8IZS8-1
	CACNA2D3	ENST00000490478.5	TSL:1	c.1501-22_1501-19delTTTT		intron	N/A	ENSP00000417279.1	Q8IZS8-2
	CACNA2D3	ENST00000468658.1	TSL:1	n.*1197-22_*1197-19delTTTT		intron	N/A	ENSP00000417455.1	F8WAV4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000632 AC: 10 AN: 158340 AF XY: 0.0000693

Gnomad AFR exome AF: 0.0000928

Gnomad AMR exome AF: 0.0000504

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000922

Gnomad FIN exome AF: 0.000158

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000271

GnomAD4 exome AF: 0.0000185 AC: 23 AN: 1243938 Hom.: 0 AF XY: 0.0000225 AC XY: 14 AN XY: 622858

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

African (AFR) AF: 0.0000723 AC: 2 AN: 27650

American (AMR) AF: 0.0000308 AC: 1 AN: 32502

Ashkenazi Jewish (ASJ) AF: 0.0000432 AC: 1 AN: 23130

East Asian (EAS) AF: 0.00 AC: 0 AN: 34746

South Asian (SAS) AF: 0.0000411 AC: 3 AN: 72926

European-Finnish (FIN) AF: 0.0000457 AC: 2 AN: 43768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4874

European-Non Finnish (NFE) AF: 0.0000137 AC: 13 AN: 952168

Other (OTH) AF: 0.0000192 AC: 1 AN: 52174

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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

Other links and lift over

dbSNP: rs35536476; hg19: chr3-54913354;