7-82005506-GAAAA-GA

Position:

• chr7-82005506-GAAAA-GA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000356860.8(CACNA2D1):​c.1516-12_1516-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,199,744 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 0.000011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: CACNA2D1 ENST00000356860.8 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 271 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4	c.1516-12_1516-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.1516-12_1516-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000722.4	ENSP00000349320

Frequencies

GnomAD3 genomes AF: 0.0000109 AC: 1 AN: 91630 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000384

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000245 AC: 271 AN: 1108114 Hom.: 0 AF XY: 0.000246 AC XY: 137 AN XY: 557006

Gnomad4 AFR exome AF: 0.000432

Gnomad4 AMR exome AF: 0.000316

Gnomad4 ASJ exome AF: 0.0000910

Gnomad4 EAS exome AF: 0.0000875

Gnomad4 SAS exome AF: 0.000159

Gnomad4 FIN exome AF: 0.0000636

Gnomad4 NFE exome AF: 0.000270

Gnomad4 OTH exome AF: 0.000169

GnomAD4 genome AF: 0.0000109 AC: 1 AN: 91630 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 44176

Gnomad4 AFR AF: 0.0000384

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs576139922; hg19: chr7-81634822;