rs1029847

Positions:

• chr7-81963904-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000722.4(CACNA2D1):​c.2780+152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 669,750 control chromosomes in the GnomAD database, including 16,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4146 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12413 hom.)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0690

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-81963904-T-C is Benign according to our data. Variant chr7-81963904-T-C is described in ClinVar as [Benign]. Clinvar id is 1226323.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4	c.2780+152A>G		intron_variant		ENST00000356860.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.2780+152A>G		intron_variant		1	NM_000722.4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34763 AN: 151814 Hom.: 4139 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.215 AC: 111498 AN: 517818 Hom.: 12413 AF XY: 0.214 AC XY: 59355 AN XY: 277172

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.229 AC: 34799 AN: 151932 Hom.: 4146 Cov.: 32 AF XY: 0.228 AC XY: 16959 AN XY: 74246

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.241

Alfa AF: 0.207 Hom.: 393

Bravo AF: 0.234

Asia WGS AF: 0.207 AC: 718 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.36

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: rs1029847; hg19: chr7-81593220; COSMIC: COSV62372126; COSMIC: COSV62372126;