Variant chr7-82136680-C-CA 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.355-5_355-4insT 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 0.102 in 1,238,188 control chromosomes in the GnomAD database, including 1,593 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 782 hom., cov: 30)

Exomes 𝑓: 0.10 ( 811 hom. )

Consequence

CACNA2D1
NM_000722.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.0210

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 7-82136680-C-CA is Benign according to our data. Variant chr7-82136680-C-CA is described in ClinVar as [Benign]. Clinvar id is 215477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4 linkuse as main transcript	c.355-5_355-4insT		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.355-5_355-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000722.4	ENSP00000349320		P54289-2

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

14369

AN:

139096

Hom.:

775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.0708

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0939

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.0777

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.136

AC:

15821

AN:

116500

Hom.:

127

AF XY:

0.131

AC XY:

8148

AN XY:

62424

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.102

AC:

112000

AN:

1099000

Hom.:

811

Cov.:

AF XY:

0.101

AC XY:

55093

AN XY:

543618

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.0768

Gnomad4 NFE exome

AF:

0.0964

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.103

AC:

14399

AN:

139188

Hom.:

782

Cov.:

AF XY:

0.104

AC XY:

6961

AN XY:

67244

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0931

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.0777

Gnomad4 OTH

AF:

0.109

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

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 11, 2018

- -

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