Variant 7-82136680-CAA-CAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000722.4(CACNA2D1):c.355-6_355-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,325,098 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 5 hom., cov: 30)

Exomes 𝑓: 0.0032 ( 9 hom. )

Consequence

CACNA2D1
NM_000722.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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-CAA is Benign according to our data. Variant chr7-82136680-C-CAA is described in ClinVar as [Benign]. Clinvar id is 220682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00324 (452/139332) while in subpopulation SAS AF= 0.0365 (160/4386). AF 95% confidence interval is 0.0319. There are 5 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 452 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D1	NM_000722.4 link	c.355-6_355-5dupTT		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.355-5_355-4insTT		splice_region_variant, intron_variant		1	NM_000722.4	ENSP00000349320.3		P54289-2

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

454

AN:

139240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00637

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000799

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00537

Gnomad SAS

AF:

0.0363

Gnomad FIN

AF:

0.000121

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000142

Gnomad OTH

AF:

0.00211

GnomAD3 exomes

AF:

0.00652

AC:

759

AN:

116500

Hom.:

AF XY:

0.00774

AC XY:

483

AN XY:

62424

show subpopulations

Gnomad AFR exome

AF:

0.00844

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00758

Gnomad SAS exome

AF:

0.0364

Gnomad FIN exome

AF:

0.000760

Gnomad NFE exome

AF:

0.000594

Gnomad OTH exome

AF:

0.00313

GnomAD4 exome

AF:

0.00322

AC:

3818

AN:

1185766

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

2270

AN XY:

587558

show subpopulations

Gnomad4 AFR exome

AF:

0.00864

Gnomad4 AMR exome

AF:

0.00272

Gnomad4 ASJ exome

AF:

0.00127

Gnomad4 EAS exome

AF:

0.00662

Gnomad4 SAS exome

AF:

0.0314

Gnomad4 FIN exome

AF:

0.000528

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00335

GnomAD4 genome

AF:

0.00324

AC:

452

AN:

139332

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

257

AN XY:

67328

show subpopulations

Gnomad4 AFR

AF:

0.00630

Gnomad4 AMR

AF:

0.000798

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00538

Gnomad4 SAS

AF:

0.0365

Gnomad4 FIN

AF:

0.000121

Gnomad4 NFE

AF:

0.000142

Gnomad4 OTH

AF:

0.00209

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Sep 03, 2020

- -

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