NM_006030.4:c.2590-11_2590-10delCT
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_006030.4(CACNA2D2):c.2590-11_2590-10delCT variant causes a intron change. The variant allele was found at a frequency of 0.000258 in 1,613,830 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 2 hom. )
Consequence
CACNA2D2
NM_006030.4 intron
NM_006030.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.17
Publications
0 publications found
Genes affected
CACNA2D2 (HGNC:1400): (calcium voltage-gated channel auxiliary subunit alpha2delta 2) Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
CACNA2D2 Gene-Disease associations (from GenCC):
- cerebellar atrophy with seizures and variable developmental delayInheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- complex neurodevelopmental disorderInheritance: AR Classification: MODERATE Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP6
Variant 3-50366634-CAG-C is Benign according to our data. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-50366634-CAG-C is described in CliVar as Benign. Clinvar id is 416540.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA2D2 | ENST00000424201.7 | c.2590-11_2590-10delCT | intron_variant | Intron 29 of 37 | 1 | NM_006030.4 | ENSP00000390329.2 | |||
CACNA2D2 | ENST00000423994.6 | c.2611-8_2611-7delCT | splice_region_variant, intron_variant | Intron 30 of 38 | 5 | ENSP00000407393.2 | ||||
CACNA2D2 | ENST00000266039.7 | c.2590-11_2590-10delCT | intron_variant | Intron 29 of 37 | 1 | ENSP00000266039.3 | ||||
CACNA2D2 | ENST00000360963.7 | c.2383-11_2383-10delCT | intron_variant | Intron 29 of 37 | 1 | ENSP00000354228.3 | ||||
ENSG00000272104 | ENST00000606589.1 | c.*9+304_*9+305delAG | intron_variant | Intron 3 of 3 | 3 | ENSP00000476225.1 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152186Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
52
AN:
152186
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.000512 AC: 128AN: 250098 AF XY: 0.000561 show subpopulations
GnomAD2 exomes
AF:
AC:
128
AN:
250098
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.000250 AC: 365AN: 1461526Hom.: 2 AF XY: 0.000268 AC XY: 195AN XY: 727024 show subpopulations
GnomAD4 exome
AF:
AC:
365
AN:
1461526
Hom.:
AF XY:
AC XY:
195
AN XY:
727024
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
221
AN:
53116
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
122
AN:
1111964
Other (OTH)
AF:
AC:
22
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
22
44
67
89
111
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
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Age
GnomAD4 genome AF: 0.000341 AC: 52AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74466 show subpopulations
GnomAD4 genome
AF:
AC:
52
AN:
152304
Hom.:
Cov.:
32
AF XY:
AC XY:
39
AN XY:
74466
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41566
American (AMR)
AF:
AC:
0
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5182
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
41
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
9
AN:
68026
Other (OTH)
AF:
AC:
1
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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>80
Age
Alfa
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Bravo
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EpiCase
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy Benign:1
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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