rs6942458

chr7-82153198-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000722.4(CACNA2D1):c.355-16522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,184 control chromosomes in the GnomAD database, including 6,504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6504 hom., cov: 27)
• Consequence: CACNA2D1 NM_000722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4	c.355-16522T>C		intron_variant		ENST00000356860.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA2D1	ENST00000356860.8	c.355-16522T>C		intron_variant		1	NM_000722.4

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42053 AN: 151066 Hom.: 6486 Cov.: 27

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42108 AN: 151184 Hom.: 6504 Cov.: 27 AF XY: 0.280 AC XY: 20654 AN XY: 73782

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.269

Alfa AF: 0.224 Hom.: 8010

Bravo AF: 0.280

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.2
Dann	Benign	0.41

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: rs6942458; hg19: chr7-81782514;