Variant 7-82066526-TAAAAA-TAA 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.659-5_659-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,430,140 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0027 ( 0 hom. )

Consequence

CACNA2D1
NM_000722.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51

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-TAAA-T is Benign according to our data. Variant chr7-82066526-TAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317982.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 83 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4 linkuse as main transcript	c.659-5_659-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000356860.8	NP_000713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8 linkuse as main transcript	c.659-5_659-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000722.4	ENSP00000349320		P54289-2

Frequencies

GnomAD3 genomes

AF:

0.000743

AC:

AN:

111720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000383

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000390

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000802

Gnomad OTH

AF:

0.00262

GnomAD3 exomes

AF:

0.0128

AC:

1162

AN:

90532

Hom.:

AF XY:

0.0127

AC XY:

617

AN XY:

48522

show subpopulations

Gnomad AFR exome

AF:

0.0255

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.0137

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.00804

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.00950

GnomAD4 exome

AF:

0.00265

AC:

3498

AN:

1318420

Hom.:

AF XY:

0.00270

AC XY:

1756

AN XY:

650940

show subpopulations

Gnomad4 AFR exome

AF:

0.00851

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.00545

Gnomad4 EAS exome

AF:

0.00401

Gnomad4 SAS exome

AF:

0.00679

Gnomad4 FIN exome

AF:

0.00472

Gnomad4 NFE exome

AF:

0.00179

Gnomad4 OTH exome

AF:

0.00332

GnomAD4 genome

AF:

0.000743

AC:

AN:

111720

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

AN XY:

52948

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000383

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000390

Gnomad4 NFE

AF:

0.0000802

Gnomad4 OTH

AF:

0.00262

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 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