Variant 7-81950516-TAAAAA-TAAAAAA 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.3160-9_3160-8insT variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0847 in 1,423,610 control chromosomes in the GnomAD database, including 2,403 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 434 hom., cov: 31)

Exomes 𝑓: 0.086 ( 1969 hom. )

Consequence

CACNA2D1
NM_000722.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.16

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 7-81950516-T-TA is Benign according to our data. Variant chr7-81950516-T-TA is described in ClinVar as [Benign]. Clinvar id is 215476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4 linkuse as main transcript	c.3160-9_3160-8insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000356860.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
CACNA2D1	ENST00000356860.8 linkuse as main transcript	c.3160-9_3160-8insT	splice_polypyrimidine_tract_variant, intron_variant	1	NM_000722.4		P54289-2
CACNA2D1	ENST00000443883.2 linkuse as main transcript	c.3196-9_3196-8insT	splice_polypyrimidine_tract_variant, intron_variant	5		P1	P54289-1
CACNA2D1	ENST00000705961.1 linkuse as main transcript	c.2927-9_2927-8insT	splice_polypyrimidine_tract_variant, intron_variant
CACNA2D1	ENST00000705962.1 linkuse as main transcript	c.3040-9_3040-8insT	splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0745

AC:

10994

AN:

147474

Hom.:

433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0673

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0921

Gnomad ASJ

AF:

0.0345

Gnomad EAS

AF:

0.0184

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.0685

Gnomad MID

AF:

0.0516

Gnomad NFE

AF:

0.0828

Gnomad OTH

AF:

0.0729

GnomAD3 exomes

AF:

0.0970

AC:

15541

AN:

160184

Hom.:

239

AF XY:

0.0949

AC XY:

8181

AN XY:

86236

show subpopulations

Gnomad AFR exome

AF:

0.0793

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.0524

Gnomad EAS exome

AF:

0.0255

Gnomad SAS exome

AF:

0.0794

Gnomad FIN exome

AF:

0.0874

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0995

GnomAD4 exome

AF:

0.0858

AC:

109545

AN:

1276046

Hom.:

1969

Cov.:

AF XY:

0.0851

AC XY:

54004

AN XY:

634724

show subpopulations

Gnomad4 AFR exome

AF:

0.0682

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.0445

Gnomad4 EAS exome

AF:

0.0216

Gnomad4 SAS exome

AF:

0.0702

Gnomad4 FIN exome

AF:

0.0757

Gnomad4 NFE exome

AF:

0.0901

Gnomad4 OTH exome

AF:

0.0824

GnomAD4 genome

AF:

0.0746

AC:

11009

AN:

147564

Hom.:

434

Cov.:

AF XY:

0.0733

AC XY:

5262

AN XY:

71820

show subpopulations

Gnomad4 AFR

AF:

0.0674

Gnomad4 AMR

AF:

0.0923

Gnomad4 ASJ

AF:

0.0345

Gnomad4 EAS

AF:

0.0184

Gnomad4 SAS

AF:

0.0605

Gnomad4 FIN

AF:

0.0685

Gnomad4 NFE

AF:

0.0828

Gnomad4 OTH

AF:

0.0727

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 12, 2018

- -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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