Variant 7-82066526-TAAAAA-TAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_000722.4(CACNA2D1):c.659-4_659-3dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,444,058 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 5 hom., cov: 27)

Exomes 𝑓: 0.0056 ( 2 hom. )

Consequence

CACNA2D1
NM_000722.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:4

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 7-82066526-T-TAA is Benign according to our data. Variant chr7-82066526-T-TAA is described in ClinVar as [Likely_benign]. Clinvar id is 1284710.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 818 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4 link	c.659-4_659-3dupTT		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.659-3_659-2insTT		splice_region_variant, intron_variant		1	NM_000722.4	ENSP00000349320.3		P54289-2

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

819

AN:

111742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00477

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000514

Gnomad SAS

AF:

0.00656

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00556

AC:

503

AN:

90532

Hom.:

AF XY:

0.00589

AC XY:

286

AN XY:

48522

show subpopulations

Gnomad AFR exome

AF:

0.00736

Gnomad AMR exome

AF:

0.00440

Gnomad ASJ exome

AF:

0.00321

Gnomad EAS exome

AF:

0.00616

Gnomad SAS exome

AF:

0.00611

Gnomad FIN exome

AF:

0.00637

Gnomad NFE exome

AF:

0.00563

Gnomad OTH exome

AF:

0.00455

GnomAD4 exome

AF:

0.00558

AC:

7428

AN:

1332338

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

3635

AN XY:

658300

show subpopulations

Gnomad4 AFR exome

AF:

0.00368

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00204

Gnomad4 EAS exome

AF:

0.00210

Gnomad4 SAS exome

AF:

0.00616

Gnomad4 FIN exome

AF:

0.00772

Gnomad4 NFE exome

AF:

0.00577

Gnomad4 OTH exome

AF:

0.00567

GnomAD4 genome

AF:

0.00732

AC:

818

AN:

111720

Hom.:

Cov.:

AF XY:

0.00774

AC XY:

410

AN XY:

52974

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000517

Gnomad4 SAS

AF:

0.00603

Gnomad4 FIN

AF:

0.0204

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.0124

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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