Variant chr7-82066526-TA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000722.4(CACNA2D1):c.659-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 111,628 control chromosomes in the GnomAD database, including 240 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 240 hom., cov: 27)

Exomes 𝑓: 0.31 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

CACNA2D1
NM_000722.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.04

Variant links:

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]

CACNA2D1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-82066526-TA-T is Benign according to our data. Variant chr7-82066526-TA-T is described in ClinVar as [Benign]. Clinvar id is 416576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-82066526-TA-T is described in Lovd as [Benign]. Variant chr7-82066526-TA-T is described in Lovd as [Likely_benign]. Variant chr7-82066526-TA-T is described in Lovd as [Benign]. Variant chr7-82066526-TA-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4 link	c.659-3delT		splice_region_variant, intron_variant		ENST00000356860.8	NP_000713.2	P54289-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8 link	c.659-3delT		splice_region_variant, intron_variant		1	NM_000722.4	ENSP00000349320.3		P54289-2

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

5259

AN:

111650

Hom.:

240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0275

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0211

Gnomad SAS

AF:

0.00428

Gnomad FIN

AF:

0.0214

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.00736

Gnomad OTH

AF:

0.0288

GnomAD3 exomes

AF:

0.337

AC:

30495

AN:

90532

Hom.:

AF XY:

0.340

AC XY:

16508

AN XY:

48522

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.311

AC:

346937

AN:

1116808

Hom.:

Cov.:

AF XY:

0.310

AC XY:

171845

AN XY:

553670

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.306

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.0472

AC:

5266

AN:

111628

Hom.:

240

Cov.:

AF XY:

0.0482

AC XY:

2551

AN XY:

52924

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.0275

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0212

Gnomad4 SAS

AF:

0.00460

Gnomad4 FIN

AF:

0.0214

Gnomad4 NFE

AF:

0.00737

Gnomad4 OTH

AF:

0.0294

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over