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Variant summary

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

The NM_000722.4(CACNA2D1):c.659-3_659-2insTTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,448,394 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 0.000018 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CACNA2D1 NM_000722.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

CACNA2D1 (HGNC:1399): (calcium voltage-gated channel auxiliary subunit alpha2delta 1) The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4	c.659-3_659-2insTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000356860.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.659-3_659-2insTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000722.4

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111752 Hom.: 0 Cov.: 27

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: 0.00

Gnomad NFE AF: 0.0000401

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000135 AC: 180 AN: 1336642 Hom.: 0 Cov.: 0 AF XY: 0.000151 AC XY: 100 AN XY: 660364

Gnomad4 AFR exome AF: 0.000141

Gnomad4 AMR exome AF: 0.000133

Gnomad4 ASJ exome AF: 0.000170

Gnomad4 EAS exome AF: 0.0000567

Gnomad4 SAS exome AF: 0.000557

Gnomad4 FIN exome AF: 0.000330

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.000127

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111752 Hom.: 0 Cov.: 27 AF XY: 0.0000189 AC XY: 1 AN XY: 52976

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000401

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs370103843; hg19: chr7-81695842;