Variant 7-81974555-GAAAA-GAAAAAA 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.1956-5_1956-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,342,172 control chromosomes in the GnomAD database, including 3,164 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 630 hom., cov: 30)

Exomes 𝑓: 0.076 ( 2534 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: -0.195

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:

CACNA2D1 (HGNC:):

CACNA2D1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-81974555-G-GAA is Benign according to our data. Variant chr7-81974555-G-GAA is described in ClinVar as [Benign]. Clinvar id is 215475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 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.1956-5_1956-4dupTT		splice_region_variant, intron_variant		ENST00000356860.8	NP_000713.2	P54289-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CACNA2D1	ENST00000356860.8 linkuse as main transcript	c.1956-5_1956-4dupTT	splice_region_variant, intron_variant	1	NM_000722.4	ENSP00000349320.3	P54289-2
CACNA2D1	ENST00000443883.2 linkuse as main transcript	c.1992-5_1992-4dupTT	splice_region_variant, intron_variant	5		ENSP00000409374.2	P54289-1H0Y715
CACNA2D1	ENST00000705962.1 linkuse as main transcript	c.1836-5_1836-4dupTT	splice_region_variant, intron_variant			ENSP00000516190.1	A0A994J595
CACNA2D1	ENST00000705961.1 linkuse as main transcript	c.1722-5_1722-4dupTT	splice_region_variant, intron_variant			ENSP00000516189.1	A0A994J5M8

Frequencies

GnomAD3 genomes

AF:

0.0923

AC:

13610

AN:

147442

Hom.:

631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0940

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.0990

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.0428

Gnomad MID

AF:

0.192

Gnomad NFE

AF:

0.0921

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.0885

AC:

17192

AN:

194206

Hom.:

446

AF XY:

0.0857

AC XY:

9015

AN XY:

105240

show subpopulations

Gnomad AFR exome

AF:

0.0933

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.0995

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.0598

Gnomad FIN exome

AF:

0.0417

Gnomad NFE exome

AF:

0.0908

Gnomad OTH exome

AF:

0.0985

GnomAD4 exome

AF:

0.0756

AC:

90358

AN:

1194648

Hom.:

2534

Cov.:

AF XY:

0.0749

AC XY:

45272

AN XY:

604160

show subpopulations

Gnomad4 AFR exome

AF:

0.0825

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0946

Gnomad4 EAS exome

AF:

0.0925

Gnomad4 SAS exome

AF:

0.0533

Gnomad4 FIN exome

AF:

0.0405

Gnomad4 NFE exome

AF:

0.0759

Gnomad4 OTH exome

AF:

0.0825

GnomAD4 genome

AF:

0.0923

AC:

13615

AN:

147524

Hom.:

630

Cov.:

AF XY:

0.0901

AC XY:

6466

AN XY:

71738

show subpopulations

Gnomad4 AFR

AF:

0.0940

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0990

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.0620

Gnomad4 FIN

AF:

0.0428

Gnomad4 NFE

AF:

0.0921

Gnomad4 OTH

AF:

0.121

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Apr 14, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 11, 2018

- -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2019

This alteration is classified as 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. -

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