rs757607965

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6_Very_StrongBP7

The NM_000722.4(CACNA2D1):c.1530G>A(p.Gly510Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,590,280 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

CACNA2D1
NM_000722.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0760

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 -9 ACMG points.

BP6

Variant 7-82005483-C-T is Benign according to our data. Variant chr7-82005483-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 220552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.076 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D1	NM_000722.4 link	c.1530G>A	p.Gly510Gly	synonymous_variant	Exon 18 of 39	ENST00000356860.8	NP_000713.2	P54289-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D1	ENST00000356860.8 link	c.1530G>A	p.Gly510Gly	synonymous_variant	Exon 18 of 39	1	NM_000722.4	ENSP00000349320.3		P54289-2

Frequencies

GnomAD3 genomes

AF:

0.000113

AC:

AN:

150556

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00113

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000159

AC:

AN:

220224

AF XY:

0.000144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.0000396

AC:

AN:

1439724

Hom.:

Cov.:

AF XY:

0.0000378

AC XY:

AN XY:

714702

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33024

American (AMR)

AF:

0.00128

AC:

AN:

42910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25598

East Asian (EAS)

AF:

0.00

AC:

AN:

39236

South Asian (SAS)

AF:

0.00

AC:

AN:

83350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097838

Other (OTH)

AF:

0.0000168

AC:

AN:

59544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000113

AC:

AN:

150556

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

73318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40856

American (AMR)

AF:

0.00113

AC:

AN:

15106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67702

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.000280

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 17, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Brugada syndrome

Benign:1

Dec 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jan 21, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

CACNA2D1-related disorder

Benign:1

Jan 27, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.076

PromoterAI

0.011

Neutral

(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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rs757607965

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over