Variant 7-81950516-TAAAAA-TAAAA 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.3160-9del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00148 in 1,413,882 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 3 hom. )

Consequence

CACNA2D1
NM_000722.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:3

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 7-81950516-TA-T is Benign according to our data. Variant chr7-81950516-TA-T is described in ClinVar as [Benign]. Clinvar id is 1165755.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-81950516-TA-T is described in Lovd as [Benign]. Variant chr7-81950516-TA-T is described in Lovd as [Likely_benign]. Variant chr7-81950516-TA-T is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 40 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA2D1	NM_000722.4 linkuse as main transcript	c.3160-9del		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.3160-9del	splice_polypyrimidine_tract_variant, intron_variant	1	NM_000722.4		P54289-2
CACNA2D1	ENST00000443883.2 linkuse as main transcript	c.3196-9del	splice_polypyrimidine_tract_variant, intron_variant	5		P1	P54289-1
CACNA2D1	ENST00000705961.1 linkuse as main transcript	c.2927-9del	splice_polypyrimidine_tract_variant, intron_variant
CACNA2D1	ENST00000705962.1 linkuse as main transcript	c.3040-9del	splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000278

AC:

AN:

147472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000996

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000680

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00395

Gnomad SAS

AF:

0.000643

Gnomad FIN

AF:

0.000728

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000900

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00956

AC:

1531

AN:

160184

Hom.:

AF XY:

0.0100

AC XY:

864

AN XY:

86236

show subpopulations

Gnomad AFR exome

AF:

0.00521

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00800

Gnomad EAS exome

AF:

0.0135

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.00540

Gnomad NFE exome

AF:

0.00857

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.00162

AC:

2054

AN:

1266320

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1143

AN XY:

629472

show subpopulations

Gnomad4 AFR exome

AF:

0.00280

Gnomad4 AMR exome

AF:

0.00801

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.00355

Gnomad4 SAS exome

AF:

0.00537

Gnomad4 FIN exome

AF:

0.00284

Gnomad4 NFE exome

AF:

0.000888

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.000271

AC:

AN:

147562

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

AN XY:

71816

show subpopulations

Gnomad4 AFR

AF:

0.0000994

Gnomad4 AMR

AF:

0.0000680

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00377

Gnomad4 SAS

AF:

0.000644

Gnomad4 FIN

AF:

0.000728

Gnomad4 NFE

AF:

0.0000900

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0196

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 15, 2023

- -

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