NM_006030.4:c.1281C>A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_006030.4(CACNA2D2):c.1281C>A(p.Ser427Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S427S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CACNA2D2
NM_006030.4 synonymous
NM_006030.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.946
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: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 3-50378973-G-T is Benign according to our data. Variant chr3-50378973-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2972919.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_006030.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| CACNA2D2 | NM_006030.4 | MANE Select | c.1281C>A | p.Ser427Ser | synonymous | Exon 13 of 38 | NP_006021.2 | ||
| CACNA2D2 | NM_001174051.3 | c.1281C>A | p.Ser427Ser | synonymous | Exon 13 of 39 | NP_001167522.1 | |||
| CACNA2D2 | NM_001005505.3 | c.1281C>A | p.Ser427Ser | synonymous | Exon 13 of 38 | NP_001005505.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CACNA2D2 | ENST00000424201.7 | TSL:1 MANE Select | c.1281C>A | p.Ser427Ser | synonymous | Exon 13 of 38 | ENSP00000390329.2 | ||
| CACNA2D2 | ENST00000423994.6 | TSL:5 | c.1281C>A | p.Ser427Ser | synonymous | Exon 13 of 39 | ENSP00000407393.2 | ||
| CACNA2D2 | ENST00000479441.1 | TSL:1 | c.1281C>A | p.Ser427Ser | synonymous | Exon 13 of 39 | ENSP00000418081.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461614Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727072 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461614
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
727072
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
1
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53150
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112010
Other (OTH)
AF:
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy Benign:1
Nov 04, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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