7-82005506-GAAAAA-GAAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000722.4(CACNA2D1):c.1516-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 91,472 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 46 hom., cov: 31)

Exomes 𝑓: 0.26 ( 28 hom. )

Failed GnomAD Quality Control

Consequence

CACNA2D1
NM_000722.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

short QT syndrome
Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
Brugada syndrome
Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
developmental and epileptic encephalopathy 110
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CACNA2D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 7-82005506-GA-G is Benign according to our data. Variant chr7-82005506-GA-G is described in ClinVar as Benign. ClinVar VariationId is 416574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D1	NM_000722.4	MANE Select	c.1516-10delT		intron	N/A	NP_000713.2
	CACNA2D1	NM_001366867.1		c.1516-10delT		intron	N/A	NP_001353796.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CACNA2D1	ENST00000356860.8	TSL:1 MANE Select	c.1516-10delT	intron	N/A	ENSP00000349320.3
CACNA2D1	ENST00000443883.2	TSL:5	c.1516-10delT	intron	N/A	ENSP00000409374.2
CACNA2D1	ENST00000705962.1		c.1432-10delT	intron	N/A	ENSP00000516190.1

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

3396

AN:

91420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.0181

Gnomad FIN

AF:

0.0386

Gnomad MID

AF:

0.0247

Gnomad NFE

AF:

0.0324

Gnomad OTH

AF:

0.0315

GnomAD2 exomes

AF:

0.286

AC:

28755

AN:

100676

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.175

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.256

AC:

223865

AN:

872830

Hom.:

Cov.:

AF XY:

0.259

AC XY:

111134

AN XY:

429818

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.241

AC:

4970

AN:

20614

American (AMR)

AF:

0.269

AC:

6043

AN:

22452

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

4329

AN:

15794

East Asian (EAS)

AF:

0.305

AC:

6718

AN:

22006

South Asian (SAS)

AF:

0.246

AC:

11827

AN:

48016

European-Finnish (FIN)

AF:

0.217

AC:

7596

AN:

34990

Middle Eastern (MID)

AF:

0.243

AC:

758

AN:

3116

European-Non Finnish (NFE)

AF:

0.256

AC:

171894

AN:

670220

Other (OTH)

AF:

0.273

AC:

9730

AN:

35622

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.290

Heterozygous variant carriers

20832

41663

62495

83326

104158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6254

12508

18762

25016

31270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0372

AC:

3399

AN:

91472

Hom.:

Cov.:

AF XY:

0.0376

AC XY:

1661

AN XY:

44122

show subpopulations

African (AFR)

AF:

0.0583

AC:

1523

AN:

26128

American (AMR)

AF:

0.0190

AC:

171

AN:

8992

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

2030

East Asian (EAS)

AF:

0.00304

AC:

AN:

2960

South Asian (SAS)

AF:

0.0185

AC:

AN:

2754

European-Finnish (FIN)

AF:

0.0386

AC:

226

AN:

5852

Middle Eastern (MID)

AF:

0.00676

AC:

AN:

148

European-Non Finnish (NFE)

AF:

0.0324

AC:

1325

AN:

40888

Other (OTH)

AF:

0.0313

AC:

AN:

1214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

151

301

452

602

753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0884

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 28, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Nov 08, 2023

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over