CACNA2D2 (Q9NY47) variants and mutations
CACNA2D2 (also known as Q9NY47) is a human protein-coding gene encoding a voltage-dependent calcium channel subunit alpha-2/delta-2 protein. It promotes trafficking and functional expression of voltage-gated calcium-channel complexes and is particularly important in cerebellar neurons. Biallelic loss-of-function variants can cause developmental epileptic encephalopathy with cerebellar atrophy and ataxia. This analysis covers 447 CACNA2D2 variants and mutations. Of these, 92% have computational variant effect predictions. Disease context includes cerebellar atrophy, developmental delay, and seizures, epilepsy, and Seizure. Example CACNA2D2 variants include P4L, G9C, and R17W.
Variant analysis overview
- Gene: CACNA2D2
- Protein: Q9NY47
- UniProt accession: Q9NY47
- Organism: Homo sapiens
- Variants analyzed: 447
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 206 unspecified-consequence records; 5 stop lost; 1 stop retained variant; 53 synonymous variants; 163 missense variants; 6 frameshift variants; 5 in-frame deletions; 5 stop-gained variants; 1 in-frame insertions; 2 splice-region variants
- Prediction scores: 412 variants have prediction scores (92% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cerebellar atrophy, developmental delay, and seizures, epilepsy, Seizure, neuropathic pain, fibromyalgia, anxiety disorder, restless legs syndrome, genetic developmental and epileptic encephalopathy, early-infantile DEE, postherpetic neuralgia, neuralgia, Focal-onset seizure.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 domains; 3 binding sites; 6 post-translational modification sites.
- Structural context: 83 variants have structural context.
- PTM context: 1 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable CACNA2D2 variants
Examples include P4L, G9C, R17W, G26D, T37P, W45*, P49R, Q66P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P4L (p.Pro4Leu), rs2471324323, ClinGen CA353000555, ClinVar RCV002304657, REVEL 0.05, MetaLR 0.02, Uncertain significance, Developmental and epileptic encephalopathy
- G9C (p.Gly9Cys), rs1699068294, ClinGen CA353000525, ClinVar RCV006560242, REVEL 0.17, MetaLR 0.03, Uncertain significance, Early-infantile DEE
- R17W (p.Arg17Trp), NCI-TCGA TCGA novel, MetaLR 0.01, MetaSVM -0.94, Uncertain significance, Developmental and epileptic encephalopathy
- G26D (p.Gly26Asp), NCI-TCGA TCGA novel, REVEL 0.03, MetaLR 0.02, Variant assessed as somatic; moderate impact.
- T37P (p.Thr37Pro), rs2471323819, ClinGen CA353000357, ClinVar RCV002692406, Uncertain significance, Inborn genetic diseases
- W45* (p.Trp45Ter), rs2471323674, ClinGen CA353000308, ClinVar RCV003338166, CADD 34.00, Likely pathogenic
- P49R (p.Pro49Arg), rs951683514, ClinGen CA353000286, ClinVar RCV006560436, REVEL 0.06, MetaLR 0.01, Uncertain significance, Early-infantile DEE
- Q66P (p.Gln66Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q79* (p.Gln79Ter), rs2471250712, ClinGen CA353002614, ClinVar RCV006559582, CADD 37.00, Pathogenic
- G83D (p.Gly83Asp), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56564, REVEL 0.11, MetaLR 0.02, Variant assessed as somatic; moderate impact.
- V84M (p.Val84Met), rs367932722, ClinGen CA2419284, ClinVar RCV000698035, ESP rs367932722, REVEL 0.15, MetaLR 0.04, Uncertain significance, Developmental and epileptic encephalopathy
- G89* (p.Gly89Ter), rs1553753355, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, Ensembl rs1553753355, CADD 37.00, Variant assessed as somatic; high impact.
- G90S (p.Gly90Ser), rs1340066055, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56569, gnomAD rs1340066055, AlphaMissense 0.28, MetaLR 0.05, Variant assessed as somatic; moderate impact.
- R95C (p.Arg95Cys), rs1456109864, TOPMed rs1456109864, gnomAD rs1456109864, REVEL 0.16, MetaLR 0.03, Variant assessed as somatic; moderate impact.
- N101S (p.Asn101Ser), rs2471148568, ClinGen CA353001277, ClinVar RCV006560622, REVEL 0.08, MetaLR 0.02, Uncertain significance, Early-infantile DEE
- R102Q (p.Arg102Gln), rs376677841, ClinGen CA2419258, cosmic curated COSV56560, ClinVar RCV006468370, REVEL 0.06, MetaLR 0.01, Uncertain significance, Early-infantile DEE
- R102W (p.Arg102Trp), rs568540115, ClinGen CA2419259, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56565, REVEL 0.17, MetaLR 0.04, Uncertain significance, Inborn genetic diseases; Developmental and epileptic encephalopathy
- E106D (p.Glu106Asp), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56561, REVEL 0.02, MetaLR 0.01, Uncertain significance, Early-infantile DEE
- N110Y (p.Asn110Tyr), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, Variant assessed as somatic; moderate impact.
- D122Y (p.Asp122Tyr), rs552824990, ClinGen CA2419247, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, REVEL 0.34, MetaLR 0.06, Uncertain significance, Developmental and epileptic encephalopathy
- Q132H (p.Gln132His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L134R (p.Leu134Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K135=, NCI-TCGA Cosmic COSV9981, Variant assessed as somatic; low impact.
- A138V (p.Ala138Val), rs35497591, ClinGen CA2419210, ClinVar RCV001054057, UniProt VAR 035048, REVEL 0.16, MetaLR 0.03, Uncertain significance, Developmental and epileptic encephalopathy
- F144Y (p.Phe144Tyr), NCI-TCGA TCGA novel, MetaLR 0.01, MetaSVM -1.06, Variant assessed as somatic; moderate impact.
- E156=, NCI-TCGA Cosmic COSV5656, Variant assessed as somatic; low impact.
- I159M (p.Ile159Met), NCI-TCGA Cosmic COSV5656, MetaLR 0.02, MetaSVM -0.99, Variant assessed as somatic; high impact.
- V160M (p.Val160Met), rs779423998, ClinGen CA2419171, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56565, REVEL 0.18, MetaLR 0.02, Conflicting interpretations, Early-infantile DEE; Inborn genetic diseases
- Y162C (p.Tyr162Cys), rs2471049368, ClinGen CA352946417, ClinVar RCV006560295, Uncertain significance, Early-infantile DEE
- K165E (p.Lys165Glu), rs1272154597, ClinGen CA352946364, ClinVar RCV006559729, TOPMed rs1272154597, AlphaMissense 0.99, MetaLR 0.08, Uncertain significance, Early-infantile DEE
- P173L (p.Pro173Leu), NCI-TCGA TCGA novel, MetaLR 0.02, MetaSVM -0.98, Variant assessed as somatic; moderate impact.
- P173S (p.Pro173Ser), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56563, REVEL 0.05, MetaLR 0.02, Variant assessed as somatic; moderate impact.
- E174K (p.Glu174Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E174Q (p.Glu174Gln), NCI-TCGA TCGA novel, MetaLR 0.01, MetaSVM -0.93, Variant assessed as somatic; moderate impact.
- E179K (p.Glu179Lys), NCI-TCGA Cosmic COSV5657, cosmic curated COSV56570, Variant assessed as somatic; moderate impact.
- S182Y (p.Ser182Tyr), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56560, MetaLR 0.02, MetaSVM -1.05, Variant assessed as somatic; moderate impact.
- S185N (p.Ser185Asn), rs969458402, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56560, Ensembl rs969458402, REVEL 0.04, AlphaMissense 0.08, Variant assessed as somatic; moderate impact.
- S185T (p.Ser185Thr), rs969458402, ClinGen CA352944610, ClinVar RCV006562498, AlphaMissense 0.08, MetaLR 0.01, Uncertain significance, Early-infantile DEE
- L187I (p.Leu187Ile), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, REVEL 0.11, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- D190Y (p.Asp190Tyr), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99816, Variant assessed as somatic; moderate impact.
- F191V (p.Phe191Val), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56560, MetaLR 0.01, MetaSVM -0.99, Variant assessed as somatic; moderate impact.
- E193K (p.Glu193Lys), rs587610576, ClinGen CA2419141, NCI-TCGA Cosmic COSV5656, ClinVar RCV001044791, REVEL 0.15, MetaLR 0.02, Uncertain significance, Developmental and epileptic encephalopathy
- N199Y (p.Asn199Tyr), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56565, Variant assessed as somatic; moderate impact.
- V201I (p.Val201Ile), rs866928902, ClinGen CA74619763, ClinVar RCV006466598, TOPMed rs866928902, REVEL 0.21, MetaLR 0.09, Uncertain significance, Early-infantile DEE
- S204L (p.Ser204Leu), rs887415177, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, Ensembl rs887415177, AlphaMissense 0.27, MetaLR 0.05, Variant assessed as somatic; moderate impact.
- A206E (p.Ala206Glu), rs770272736, ClinGen CA352943955, ClinVar RCV006558821, AlphaMissense 0.37, MetaLR 0.02, Uncertain significance, Early-infantile DEE
- P211S (p.Pro211Ser), rs587771507, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, 1000Genomes rs587771507, REVEL 0.75, MetaLR 0.12, Variant assessed as somatic; moderate impact.
- Y215C (p.Tyr215Cys), NCI-TCGA TCGA novel, MetaLR 0.09, MetaSVM -1.04, Variant assessed as somatic; moderate impact.
- G217D (p.Gly217Asp), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56561, MetaLR 0.07, MetaSVM -1.15, Variant assessed as somatic; moderate impact.
- L231V (p.Leu231Val), rs587617827, ClinGen CA352940516, ClinVar RCV006560460, REVEL 0.33, MetaLR 0.11, Uncertain significance, Early-infantile DEE
- E232Q (p.Glu232Gln), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99816, MetaLR 0.01, MetaSVM -0.96, Variant assessed as somatic; moderate impact.
- M236R (p.Met236Arg), rs2471034581, ClinGen CA352940278, ClinVar RCV006560463, Uncertain significance, Early-infantile DEE
- E237Q (p.Glu237Gln), rs1553730554, ClinGen CA352940230, ClinVar RCV006560292, Uncertain significance, Early-infantile DEE
- R239H (p.Arg239His), rs201610016, ClinGen CA2419096, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56561, REVEL 0.09, MetaLR 0.02, Uncertain significance, Inborn genetic diseases; Developmental and epileptic encephalopathy
- Q248* (p.Gln248Ter), rs1310940542, gnomAD rs1310940542, Variant assessed as somatic; high impact.
- S252C (p.Ser252Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R258C (p.Arg258Cys), rs770337861, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56566, ExAC rs770337861, REVEL 0.42, MetaLR 0.14, Variant assessed as somatic; moderate impact.
- R258L (p.Arg258Leu), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56567, NCI-TCGA Cosmic COSV9981, REVEL 0.39, MetaLR 0.09, Variant assessed as somatic; moderate impact.
- P261L (p.Pro261Leu), rs1211603072, ClinGen CA352939391, cosmic curated COSV56563, ClinVar RCV000636384, REVEL 0.66, MetaLR 0.46, Uncertain significance, not specified; Developmental and epileptic encephalopathy; Inborn genetic diseas
- R266Q (p.Arg266Gln), rs1288650707, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56564, Ensembl rs1288650707, REVEL 0.22, AlphaMissense 0.07, Variant assessed as somatic; moderate impact.
- K269N (p.Lys269Asn), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99816, REVEL 0.11, MetaLR 0.00, Variant assessed as somatic; moderate impact.
- D272E (p.Asp272Glu), rs1441229685, ClinGen CA352939068, ClinVar RCV003993579, REVEL 0.27, MetaLR 0.07, Uncertain significance, Cerebellar atrophy with seizures and variable developmental delay
- V276I (p.Val276Ile), rs1192786729, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56563, gnomAD rs1192786729, REVEL 0.22, AlphaMissense 0.08, Variant assessed as somatic; moderate impact.
- G285E (p.Gly285Glu), rs2471031468, ClinGen CA352938746, ClinVar RCV004432324, Uncertain significance, Inborn genetic diseases
- E316K (p.Glu316Lys), rs769033285, ClinGen CA2419019, NCI-TCGA Cosmic COSV5657, cosmic curated COSV56570, REVEL 0.65, MetaLR 0.38, Uncertain significance, Early-infantile DEE; Inborn genetic diseases
- L318R (p.Leu318Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S322A (p.Ser322Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S331=, rs780661542, NCI-TCGA Cosmic COSV5656, Variant assessed as somatic; low impact.
- F332=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- E334K (p.Glu334Lys), rs743855, ClinGen CA74615594, ClinVar RCV001296063, UniProt VAR 057782, REVEL 0.14, MetaLR 0.03, Uncertain significance, Developmental and epileptic encephalopathy
- N349T (p.Asn349Thr), NCI-TCGA TCGA novel, MetaLR 0.54, MetaSVM 0.07, Variant assessed as somatic; moderate impact.
- R351H (p.Arg351His), rs747629573, ClinGen CA2418994, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56562, REVEL 0.59, MetaLR 0.64, Uncertain significance, Developmental and epileptic encephalopathy; Inborn genetic diseases
- A359V (p.Ala359Val), NCI-TCGA TCGA novel, MetaLR 0.12, MetaSVM -1.01, Variant assessed as somatic; moderate impact.
- V364M (p.Val364Met), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56565, REVEL 0.35, MetaLR 0.56, Variant assessed as somatic; moderate impact.
- Y371C (p.Tyr371Cys), rs1705182962, UniProt VAR 085040, Ensembl rs1705182962, REVEL 0.88, MetaLR 0.70, Uncertain significance
- E376* (p.Glu376Ter), rs2471029525, ClinGen CA352935431, ClinVar RCV002471683, CADD 37.00, Pathogenic
- A378S (p.Ala378Ser), rs2471029504, ClinGen CA352935319, ClinVar RCV006560706, Uncertain significance, Early-infantile DEE
- M395I (p.Met395Ile), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, MetaLR 0.23, MetaSVM -0.78, Variant assessed as somatic; moderate impact.
- M397V (p.Met397Val), rs142559701, ClinGen CA2418950, cosmic curated COSV56564, ClinVar RCV006466305, REVEL 0.80, MetaLR 0.52, Uncertain significance, Early-infantile DEE
- D405G (p.Asp405Gly), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56561, MetaLR 0.04, MetaSVM -1.10, Variant assessed as somatic; moderate impact.
- R406H (p.Arg406His), rs752852530, ClinGen CA2418946, ClinVar RCV000540272, ExAC rs752852530, REVEL 0.19, MetaLR 0.09, Uncertain significance, Developmental and epileptic encephalopathy
- R406S (p.Arg406Ser), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, Variant assessed as somatic; moderate impact.
- Y414C (p.Tyr414Cys), NCI-TCGA TCGA novel, MetaLR 0.10, MetaSVM -0.97, Variant assessed as somatic; moderate impact.
- T420M (p.Thr420Met), rs781210506, ClinGen CA74615280, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, REVEL 0.30, MetaLR 0.07, Uncertain significance, Developmental and epileptic encephalopathy
- R422C (p.Arg422Cys), rs1705146191, ClinGen CA352931693, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56560, REVEL 0.91, MetaLR 0.74, Uncertain significance, Cerebellar atrophy with seizures and variable developmental delay; Early-infanti
- F426L (p.Phe426Leu), NCI-TCGA TCGA novel, MetaLR 0.70, MetaSVM 0.53, Variant assessed as somatic; moderate impact.
- S427F (p.Ser427Phe), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56562, REVEL 0.82, MetaLR 0.66, Variant assessed as somatic; moderate impact.
- V428M (p.Val428Met), rs748093850, ClinGen CA2418912, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99816, REVEL 0.72, MetaLR 0.72, Uncertain significance, Early-infantile DEE
- N432K (p.Asn432Lys), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56561, MetaLR 0.65, MetaSVM 0.40, Variant assessed as somatic; moderate impact.
- Y433D (p.Tyr433Asp), rs2471027523, ClinGen CA352931352, ClinVar RCV006559800, Uncertain significance, Early-infantile DEE
- P437S (p.Pro437Ser), NCI-TCGA TCGA novel, REVEL 0.64, MetaLR 0.67, Variant assessed as somatic; moderate impact.
- N445I (p.Asn445Ile), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, TOPMed rs1705139448, MetaLR 0.11, MetaSVM -0.91, Variant assessed as somatic; moderate impact.
- P453S (p.Pro453Ser), rs2471025515, ClinGen CA352930442, ClinVar RCV003143944, REVEL 0.51, MetaLR 0.44, Uncertain significance, Cerebellar atrophy with seizures and variable developmental delay
- E464K (p.Glu464Lys), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, Variant assessed as somatic; moderate impact.
- L466I (p.Leu466Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G477D (p.Gly477Asp), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56562, NCI-TCGA Cosmic COSV9981, MetaLR 0.03, MetaSVM -1.05, Variant assessed as somatic; moderate impact.
- L493=, NCI-TCGA Cosmic COSV5656, Variant assessed as somatic; low impact.
- G494R (p.Gly494Arg), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56564, Variant assessed as somatic; moderate impact.
- G496W (p.Gly496Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G501E (p.Gly501Glu), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, Variant assessed as somatic; moderate impact.
- N507S (p.Asn507Ser), NCI-TCGA TCGA novel, TOPMed rs1705066492, REVEL 0.19, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- L522M (p.Leu522Met), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56569, Variant assessed as somatic; moderate impact.
- V524L (p.Val524Leu), rs758052476, ClinGen CA352927670, ClinVar RCV006559699, AlphaMissense 0.92, MetaLR 0.28, Uncertain significance, Early-infantile DEE
- V524M (p.Val524Met), rs758052476, ClinGen CA2418809, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56564, REVEL 0.52, AlphaMissense 0.92, Uncertain significance, Inborn genetic diseases; Cerebellar atrophy with seizures and variable developme
- P539S (p.Pro539Ser), rs1705051616, ClinGen CA352927256, ClinVar RCV006559732, AlphaMissense 0.39, MetaLR 0.06, Uncertain significance, Early-infantile DEE
- A545T (p.Ala545Thr), rs1200566757, ClinGen CA352925676, ClinVar RCV002836871, AlphaMissense 0.23, MetaLR 0.03, Uncertain significance, Inborn genetic diseases
- F550L (p.Phe550Leu), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, MetaLR 0.19, MetaSVM -0.71, Variant assessed as somatic; moderate impact.
- V558A (p.Val558Ala), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, MetaLR 0.08, MetaSVM -1.07, Variant assessed as somatic; moderate impact.
- P574S (p.Pro574Ser), rs2471017963, ClinGen CA352925022, ClinVar RCV006559986, Uncertain significance, Early-infantile DEE
- V575M (p.Val575Met), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56569, REVEL 0.23, MetaLR 0.06, Variant assessed as somatic; moderate impact.
- T576N (p.Thr576Asn), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, MetaLR 0.04, MetaSVM -1.14, Variant assessed as somatic; moderate impact.
- D578E (p.Asp578Glu), rs1482667522, ClinGen CA352924939, ClinVar RCV006559912, Uncertain significance, Early-infantile DEE
- D581N (p.Asp581Asn), rs1419557043, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, TOPMed rs1419557043, AlphaMissense 0.92, MetaLR 0.69, Variant assessed as somatic; moderate impact.
- I592=, NCI-TCGA Cosmic COSV5656, Variant assessed as somatic; low impact.
- G599V (p.Gly599Val), NCI-TCGA Cosmic COSV5657, cosmic curated COSV56570, MetaLR 0.74, MetaSVM 0.62, Variant assessed as somatic; moderate impact.
- G602S (p.Gly602Ser), rs2471017313, ClinGen CA352924324, ClinVar RCV003588970, Uncertain significance, Developmental and epileptic encephalopathy
- V610A (p.Val610Ala), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, MetaLR 0.43, MetaSVM -0.20, Variant assessed as somatic; moderate impact.
- E615G (p.Glu615Gly), NCI-TCGA TCGA novel, MetaLR 0.67, MetaSVM 0.32, Variant assessed as somatic; moderate impact.
- Y625C (p.Tyr625Cys), rs780181502, ClinGen CA2418691, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, REVEL 0.92, MetaLR 0.70, Uncertain significance, Inborn genetic diseases; Developmental and epileptic encephalopathy; Cerebellar
- Y635* (p.Tyr635Ter), rs1322090113, ClinGen CA352923401, ClinVar RCV006563022, Pathogenic
- F647V (p.Phe647Val), rs2471014544, ClinGen CA352922086, ClinVar RCV002860731, REVEL 0.27, MetaLR 0.26, Uncertain significance, Inborn genetic diseases
- L653R (p.Leu653Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E679Q (p.Glu679Gln), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, Variant assessed as somatic; moderate impact.
- E690K (p.Glu690Lys), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56563, Variant assessed as somatic; moderate impact.
- D694N (p.Asp694Asn), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, MetaLR 0.04, MetaSVM -1.05, Variant assessed as somatic; moderate impact.
- S698L (p.Ser698Leu), rs2470992599, ClinGen CA352916453, ClinVar RCV006471869, Uncertain significance, Early-infantile DEE
- F704L (p.Phe704Leu), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, MetaLR 0.03, MetaSVM -1.16, Variant assessed as somatic; moderate impact.
- F708C (p.Phe708Cys), NCI-TCGA TCGA novel, MetaLR 0.25, MetaSVM -0.74, Variant assessed as somatic; moderate impact.
- T716A (p.Thr716Ala), NCI-TCGA TCGA novel, MetaLR 0.34, MetaSVM -0.26, Variant assessed as somatic; moderate impact.
- D718N (p.Asp718Asn), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56564, MetaLR 0.17, MetaSVM -1.00, Variant assessed as somatic; moderate impact.
- F725L (p.Phe725Leu), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, MetaLR 0.43, MetaSVM -0.26, Variant assessed as somatic; moderate impact.
- T734M (p.Thr734Met), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, TOPMed rs1704427096, Variant assessed as somatic; moderate impact.
- I736V (p.Ile736Val), rs2470990539, ClinGen CA352915309, ClinVar RCV006471520, Uncertain significance, Early-infantile DEE
- R743C (p.Arg743Cys), rs2109411511, ClinGen CA352915102, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56561, AlphaMissense 0.50, MetaLR 0.35, Uncertain significance, Early-infantile DEE
- R743H (p.Arg743His), rs768385122, ClinGen CA2418564, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, AlphaMissense 0.11, MetaLR 0.30, Uncertain significance, Inborn genetic diseases; Developmental and epileptic encephalopathy
- D749N (p.Asp749Asn), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, Variant assessed as somatic; moderate impact.
- D763E (p.Asp763Glu), rs375235408, ClinGen CA352914373, ClinVar RCV003481700, Uncertain significance, not provided
- G764S (p.Gly764Ser), rs906863087, ClinGen CA74608051, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56563, AlphaMissense 0.31, MetaLR 0.50, Uncertain significance, Developmental and epileptic encephalopathy
- N772Q (p.Asn772Gln), NCI-TCGA TCGA novel, MetaLR 0.10, MetaSVM -0.96, Variant assessed as somatic; high impact.
- E776K (p.Glu776Lys), NCI-TCGA TCGA novel, TOPMed rs1553726203, Variant assessed as somatic; moderate impact.
- D777N (p.Asp777Asn), rs2470988430, ClinGen CA352913876, ClinVar RCV006559679, Uncertain significance, Early-infantile DEE
- P782L (p.Pro782Leu), rs2470988341, ClinGen CA352913681, ClinVar RCV006560303, Uncertain significance, Early-infantile DEE
- Y790C (p.Tyr790Cys), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99816, MetaLR 0.16, MetaSVM -1.00, Variant assessed as somatic; moderate impact.
- R791L (p.Arg791Leu), NCI-TCGA Cosmic COSV9981, Variant assessed as somatic; moderate impact.
- R792H (p.Arg792His), rs1011668282, ClinGen CA74607855, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56562, AlphaMissense 0.69, MetaLR 0.63, Uncertain significance, Developmental and epileptic encephalopathy; Inborn genetic diseases
- H797Y (p.His797Tyr), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99816, Variant assessed as somatic; moderate impact.
- P804H (p.Pro804His), NCI-TCGA TCGA novel, MetaLR 0.14, MetaSVM -1.00, Variant assessed as somatic; high impact.
- R811K (p.Arg811Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G833C (p.Gly833Cys), rs1210463730, ClinGen CA352911692, ClinVar RCV003309671, AlphaMissense 0.26, MetaLR 0.42, Uncertain significance, Inborn genetic diseases
- R835C (p.Arg835Cys), rs774552132, ClinGen CA2418473, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56567, AlphaMissense 0.38, MetaLR 0.38, Conflicting interpretations, Cerebellar atrophy with seizures and variable developmental delay; Inborn geneti
- V841M (p.Val841Met), rs2470985523, ClinGen CA352911403, ClinVar RCV006559744, Uncertain significance, Early-infantile DEE
- A850S (p.Ala850Ser), NCI-TCGA TCGA novel, MetaLR 0.29, MetaSVM -0.65, Variant assessed as somatic; moderate impact.
- A852V (p.Ala852Val), rs1298263050, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56563, gnomAD rs1298263050, REVEL 0.48, MetaLR 0.40, Variant assessed as somatic; moderate impact.
- R862C (p.Arg862Cys), rs1302325175, ClinGen CA352910509, ClinVar RCV002599528, gnomAD rs1302325175, AlphaMissense 0.40, MetaLR 0.26, Uncertain significance, Developmental and epileptic encephalopathy
- R862H (p.Arg862His), rs771678835, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99817, ExAC rs771678835, AlphaMissense 0.08, MetaLR 0.21, Uncertain significance, Inborn genetic diseases
- Q867H (p.Gln867His), NCI-TCGA TCGA novel, MetaLR 0.30, MetaSVM -0.77, Variant assessed as somatic; moderate impact.
- C871=, rs1179657650, NCI-TCGA Cosmic COSV5656, Variant assessed as somatic; low impact.
- C871R (p.Cys871Arg), rs2470983610, ClinGen CA352907733, ClinVar RCV004432322, Uncertain significance, Inborn genetic diseases
- M879I (p.Met879Ile), rs1286525418, ClinGen CA352907482, ClinVar RCV006558813, gnomAD rs1286525418, AlphaMissense 0.96, MetaLR 0.46, Uncertain significance, Early-infantile DEE
- M879L (p.Met879Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M879V (p.Met879Val), NCI-TCGA TCGA novel, MetaLR 0.21, MetaSVM -0.71, Variant assessed as somatic; moderate impact.
- D880N (p.Asp880Asn), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56566, MetaLR 0.22, MetaSVM -0.79, Variant assessed as somatic; moderate impact.
- E882K (p.Glu882Lys), rs140562117, ClinGen CA2418423, cosmic curated COSV56563, ClinVar RCV001344977, AlphaMissense 0.47, MetaLR 0.28, Uncertain significance, Developmental and epileptic encephalopathy
- V883A (p.Val883Ala), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, Variant assessed as somatic; moderate impact.
- V883F (p.Val883Phe), rs140305683, ClinGen CA352907348, ClinVar RCV003990906, AlphaMissense 0.10, MetaLR 0.33, Uncertain significance, Cerebellar atrophy with seizures and variable developmental delay
- E886Q (p.Glu886Gln), NCI-TCGA Cosmic COSV5657, cosmic curated COSV56570, Variant assessed as somatic; moderate impact.
- V891F (p.Val891Phe), rs2470981530, ClinGen CA352906937, ClinVar RCV006560170, Uncertain significance, Early-infantile DEE
- G897A (p.Gly897Ala), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, MetaLR 0.56, MetaSVM 0.17, Variant assessed as somatic; moderate impact.
- N903S (p.Asn903Ser), NCI-TCGA Cosmic COSV5656, cosmic curated COSV56566, MetaLR 0.35, MetaSVM -0.27, Variant assessed as somatic; moderate impact.
- H906N (p.His906Asn), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, Variant assessed as somatic; moderate impact.
- F914L (p.Phe914Leu), NCI-TCGA TCGA novel, 1000Genomes rs140117542, ESP rs140117542, ExAC rs140117542, MetaLR 0.22, MetaSVM -0.76, Likely benign
- N928K (p.Asn928Lys), NCI-TCGA TCGA novel, MetaLR 0.33, MetaSVM -0.50, Variant assessed as somatic; moderate impact.
- A945T (p.Ala945Thr), NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, Variant assessed as somatic; moderate impact.
- G953S (p.Gly953Ser), rs2109402396, ClinGen CA352904364, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99816, AlphaMissense 0.18, MetaLR 0.42, Uncertain significance, Early-infantile DEE
- R957Q (p.Arg957Gln), rs1333604942, NCI-TCGA Cosmic COSV5656, cosmic curated COSV56568, gnomAD rs1333604942, AlphaMissense 0.21, MetaLR 0.52, Variant assessed as somatic; moderate impact.
- R957W (p.Arg957Trp), rs1209696501, ClinGen CA352904166, NCI-TCGA Cosmic COSV9981, ClinVar RCV000795902, AlphaMissense 0.36, MetaLR 0.49, Uncertain significance, Developmental and epileptic encephalopathy; Inborn genetic diseases; not provide
- F960L (p.Phe960Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- F960V (p.Phe960Val), NCI-TCGA TCGA novel, MetaLR 0.13, MetaSVM -0.92, Variant assessed as somatic; moderate impact.
- V964I (p.Val964Ile), rs1704238712, ClinGen CA352903732, NCI-TCGA Cosmic COSV9981, cosmic curated COSV99818, AlphaMissense 0.07, MetaLR 0.10, Uncertain significance, Early-infantile DEE
- D966Y (p.Asp966Tyr), NCI-TCGA TCGA novel, MetaLR 0.69, MetaSVM 0.33, Variant assessed as somatic; moderate impact.
Public CACNA2D2 analysis runs
- CACNA2D2 analysis run — CACNA2D2 (447 variants) — completed 2026-08-19