chr7-82136680-C-CA

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.355-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 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, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.0210

Publications

1 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 7-82136680-C-CA is Benign according to our data. Variant chr7-82136680-C-CA is described in ClinVar as Benign. ClinVar VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CACNA2D1	NM_000722.4	MANE Select	c.355-5dupT	splice_region intron	N/A	NP_000713.2
CACNA2D1	NM_001366867.1		c.355-5dupT	splice_region intron	N/A	NP_001353796.1
CACNA2D1	NM_001302890.2		c.355-5dupT	splice_region intron	N/A	NP_001289819.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CACNA2D1	ENST00000356860.8	TSL:1 MANE Select	c.355-5_355-4insT	splice_region intron	N/A	ENSP00000349320.3
CACNA2D1	ENST00000423588.1	TSL:1	c.355-5_355-4insT	splice_region intron	N/A	ENSP00000405395.1
CACNA2D1	ENST00000443883.2	TSL:5	c.355-5_355-4insT	splice_region intron	N/A	ENSP00000409374.2

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

GnomAD2 exomes

AF:

0.136

AC:

15821

AN:

116500

AF XY:

0.131

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 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

African (AFR)

AF:

0.171

AC:

4328

AN:

25290

American (AMR)

AF:

0.143

AC:

4245

AN:

29636

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

2412

AN:

18530

East Asian (EAS)

AF:

0.152

AC:

4315

AN:

28480

South Asian (SAS)

AF:

0.102

AC:

6076

AN:

59772

European-Finnish (FIN)

AF:

0.0768

AC:

2648

AN:

34466

Middle Eastern (MID)

AF:

0.171

AC:

781

AN:

4562

European-Non Finnish (NFE)

AF:

0.0964

AC:

82295

AN:

853622

Other (OTH)

AF:

0.110

AC:

4900

AN:

44642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

3710

7420

11130

14840

18550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3314

6628

9942

13256

16570

<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:

0.103

AC:

14399

AN:

139188

Hom.:

782

Cov.:

AF XY:

0.104

AC XY:

6961

AN XY:

67244

show subpopulations

African (AFR)

AF:

0.151

AC:

5770

AN:

38220

American (AMR)

AF:

0.108

AC:

1485

AN:

13764

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

369

AN:

3282

East Asian (EAS)

AF:

0.110

AC:

532

AN:

4832

South Asian (SAS)

AF:

0.0931

AC:

408

AN:

4382

European-Finnish (FIN)

AF:

0.0694

AC:

571

AN:

8224

Middle Eastern (MID)

AF:

0.241

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0777

AC:

4926

AN:

63418

Other (OTH)

AF:

0.109

AC:

209

AN:

1912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

591

1181

1772

2362

2953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0572

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:1

Jun 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Brugada syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.021

Mutation Taster

=100/0

polymorphism (auto)

(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

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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