CCND2 (G1/S-specific cyclin-D2) variants and mutations
CCND2 (also known as G1/S-specific cyclin-D2) is a human protein-coding gene encoding a g1/S-specific cyclin-D2 protein. It promotes G1-to-S cell-cycle progression through activation of CDK4 and CDK6 and is important in proliferating neural and endocrine tissues. Activating germline variants can cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, while overexpression occurs in several cancers. This analysis covers 578 CCND2 variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus, and neurodegenerative disease. Example CCND2 variants include E2*, E2V, and L3V.
Variant analysis overview
- Gene: CCND2
- Protein: G1/S-specific cyclin-D2
- UniProt accession: P30279
- Organism: Homo sapiens
- Variants analyzed: 578
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 404 unspecified-consequence records; 89 synonymous variants; 69 missense variants; 1 in-frame deletions; 3 frameshift variants; 5 splice-region variants; 3 stop-gained variants; 4 substitution
- Prediction scores: 432 variants have prediction scores (75% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus, neurodegenerative disease, hereditary disease, diabetes mellitus, type 2 diabetes mellitus, colorectal cancer, megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, diabetic eye disease, colorectal adenocarcinoma, B-cell chronic lymphocytic leukemia, colon adenocarcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 post-translational modification sites.
- Structural context: 261 variants have structural context.
- PTM context: 7 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 CCND2 variants
Examples include E2*, E2V, L3V, L3L, L3M, L3P, L4M, C5F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2* (p.Glu2Ter), gnomAD rs1219274844
- E2V (p.Glu2Val), gnomAD rs1278580204
- L3V (p.Leu3Val), TOPMed rs904703881, gnomAD rs904703881
- L3L (p.Leu3Leu), rs904703881, gnomAD 12-4274047-C-T, CADD 12.70
- L3M (p.Leu3Met), gnomAD 12-4274047-C-A, REVEL 0.26, MetaLR 0.14
- L3P (p.Leu3Pro), gnomAD 12-4274048-T-C, REVEL 0.40, MetaLR 0.14
- L4M (p.Leu4Met), ExAC rs774670428, TOPMed rs774670428, gnomAD rs774670428
- C5F (p.Cys5Phe), ExAC rs745641213, gnomAD rs745641213, REVEL 0.56, MetaLR 0.13
- C5R (p.Cys5Arg), gnomAD rs1211080900, REVEL 0.52, MetaLR 0.12
- C5C (p.Cys5Cys), rs771959269, gnomAD 12-4274055-C-T, CADD 12.90
- H6P (p.His6Pro), Ensembl rs2120513029
- H6Q (p.His6Gln), ExAC rs775161299, gnomAD rs775161299, REVEL 0.05, MetaLR 0.01
- H6L (p.His6Leu), gnomAD 12-4274057-A-T, REVEL 0.06, MetaLR 0.01
- E7K (p.Glu7Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E7D (p.Glu7Asp), gnomAD 12-4274061-G-C, REVEL 0.23, MetaLR 0.13
- V8G (p.Val8Gly), Ensembl rs2120513079
- V8M (p.Val8Met), ESP rs370617608, ExAC rs370617608, TOPMed rs370617608, gnomAD rs370617608, REVEL 0.09, MetaLR 0.02
- V8V (p.Val8Val), rs553724162, gnomAD 12-4274064-G-A, CADD 13.80
- D9A (p.Asp9Ala), TOPMed rs1374564893, gnomAD rs1374564893
- D9E (p.Asp9Glu), gnomAD rs1863825137
- D9G (p.Asp9Gly), rs1374564893, NCI-TCGA Cosmic COSV9971, TOPMed rs1374564893, gnomAD rs1374564893, REVEL 0.22, MetaLR 0.07, Uncertain significance, not provided
- D9H (p.Asp9His), ExAC rs776260684, gnomAD rs776260684, REVEL 0.24, MetaLR 0.08, Uncertain significance
- D9V (p.Asp9Val), TOPMed rs1374564893, gnomAD rs1374564893
- D9Y (p.Asp9Tyr), rs776260684, ClinGen CA6395139, ClinVar RCV003680068, ExAC rs776260684, REVEL 0.36, MetaLR 0.08, Uncertain significance, not provided
- D9D (p.Asp9Asp), rs1863825137, gnomAD 12-4274067-C-T, CADD 14.40
- P10L (p.Pro10Leu), 1000Genomes rs200897111, ExAC rs200897111, TOPMed rs200897111, gnomAD rs200897111, REVEL 0.10, MetaLR 0.02, Uncertain significance, Inborn genetic diseases
- P10R (p.Pro10Arg), gnomAD 12-4274069-C-G, REVEL 0.10, MetaLR 0.01
- P10P (p.Pro10Pro), rs1335185877, gnomAD 12-4274070-G-C, CADD 13.30
- V11A (p.Val11Ala), Ensembl rs2120513185
- V11I (p.Val11Ile), Ensembl rs2120513171
- V11V (p.Val11Val), rs371641860, gnomAD 12-4274073-C-T, CADD 13.80
- R12H (p.Arg12His), TOPMed rs1863825351
- R12P (p.Arg12Pro), TOPMed rs1863825351
- R12L (p.Arg12Leu), gnomAD 12-4274075-G-T, REVEL 0.11, MetaLR 0.02
- R12R (p.Arg12Arg), rs374125669, gnomAD 12-4274076-C-T, CADD 16.30
- A14G (p.Ala14Gly), gnomAD rs1278982864
- A14T (p.Ala14Thr), Ensembl rs2120513221
- A14V (p.Ala14Val), gnomAD rs1278982864
- A14A (p.Ala14Ala), gnomAD 12-4274082-C-T, CADD 14.00
- V15A (p.Val15Ala), gnomAD rs1242864601, REVEL 0.11, MetaLR 0.01
- V15G (p.Val15Gly), gnomAD rs1242864601, REVEL 0.13, MetaLR 0.01
- V15L (p.Val15Leu), gnomAD rs1374736402, REVEL 0.08, MetaLR 0.01
- V15M (p.Val15Met), gnomAD rs1374736402, REVEL 0.10, MetaLR 0.01
- V15E (p.Val15Glu), gnomAD 12-4274084-T-A, REVEL 0.15, MetaLR 0.01
- V15V (p.Val15Val), rs1301716232, gnomAD 12-4274085-G-A, CADD 13.40
- R16W (p.Arg16Trp), ExAC rs750148470, TOPMed rs750148470, gnomAD rs750148470, REVEL 0.10, MetaLR 0.02
- R16R (p.Arg16Arg), rs750148470, gnomAD 12-4274086-C-A, CADD 15.50
- R16L (p.Arg16Leu), gnomAD 12-4274087-G-T, REVEL 0.10, MetaLR 0.01
- D17D (p.Asp17Asp), rs2120513286, gnomAD 12-4274091-C-T, CADD 14.80
- R18C (p.Arg18Cys), 1000Genomes rs535993641, ExAC rs535993641, TOPMed rs535993641, gnomAD rs535993641, REVEL 0.06, MetaLR 0.02
- R18G (p.Arg18Gly), 1000Genomes rs535993641, ExAC rs535993641, TOPMed rs535993641, gnomAD rs535993641, REVEL 0.07, MetaLR 0.02
- R18H (p.Arg18His), ExAC rs753037343, TOPMed rs753037343, gnomAD rs753037343, REVEL 0.08, MetaLR 0.01
- R18P (p.Arg18Pro), gnomAD 12-4274093-G-C, REVEL 0.06, MetaLR 0.00
- N19I (p.Asn19Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N19K (p.Asn19Lys), NCI-TCGA Cosmic COSV5422, Variant assessed as somatic; moderate impact.
- N19T (p.Asn19Thr), Ensembl rs2120513319
- N19D (p.Asn19Asp), gnomAD 12-4274095-A-G, REVEL 0.12, MetaLR 0.03
- N19S (p.Asn19Ser), gnomAD 12-4274096-A-G, REVEL 0.11, MetaLR 0.02
- L20L (p.Leu20Leu), gnomAD 12-4274098-C-T, CADD 14.90
- L21F (p.Leu21Phe), gnomAD 12-4274101-C-T, REVEL 0.04, CADD 24.80
- R22G (p.Arg22Gly), ExAC rs778299007, TOPMed rs778299007, gnomAD rs778299007, REVEL 0.02, MetaLR 0.02
- R22Q (p.Arg22Gln), 1000Genomes rs556058578, ExAC rs556058578, TOPMed rs556058578, gnomAD rs556058578, REVEL 0.01, MetaLR 0.02, Likely benign, Inborn genetic diseases
- D23H (p.Asp23His), Ensembl rs2120513394
- D23D (p.Asp23Asp), rs757391391, gnomAD 12-4274109-C-T, CADD 13.20
- D24E (p.Asp24Glu), TOPMed rs1232891371, gnomAD rs1232891371, REVEL 0.16, MetaLR 0.04
- D24Y (p.Asp24Tyr), gnomAD 12-4274110-G-T, REVEL 0.37, CADD 31.00
- R25H (p.Arg25His), Ensembl rs2120513452
- R25S (p.Arg25Ser), Ensembl rs2120513439
- R25R (p.Arg25Arg), gnomAD 12-4274115-C-T, CADD 14.90
- V26I (p.Val26Ile), Ensembl rs2120513477
- V26V (p.Val26Val), gnomAD 12-4274118-C-T, CADD 8.55
- L27L (p.Leu27Leu), rs1157141448, gnomAD 12-4274119-C-T, CADD 9.39
- Q28E (p.Gln28Glu), Ensembl rs1418862467
- Q28H (p.Gln28His), TOPMed rs1863826707
- Q28K (p.Gln28Lys), Ensembl rs1418862467, Uncertain significance, Inborn genetic diseases
- Q28L (p.Gln28Leu), TOPMed rs1863826668
- N29H (p.Asn29His), TOPMed rs1368834606
- L30M (p.Leu30Met), rs778986120, ClinGen CA6395150, ClinVar RCV002934417, ExAC rs778986120, REVEL 0.23, MetaLR 0.04, Uncertain significance, Inborn genetic diseases
- L30L (p.Leu30Leu), gnomAD 12-4274128-C-T, CADD 8.96
- L31F (p.Leu31Phe), ExAC rs746043858, TOPMed rs746043858, gnomAD rs746043858, REVEL 0.28, MetaLR 0.15
- L31V (p.Leu31Val), ExAC rs746043858, TOPMed rs746043858, gnomAD rs746043858, REVEL 0.30, MetaLR 0.12
- L31L (p.Leu31Leu), gnomAD 12-4274133-C-G, CADD 13.30
- T32A (p.Thr32Ala), rs772187536, ClinGen CA6395152, ClinVar RCV002576981, ClinVar RCV005433841, REVEL 0.19, MetaLR 0.01, Conflicting interpretations, not provided; not specified
- T32T (p.Thr32Thr), rs779857983, gnomAD 12-4274136-C-T, CADD 14.70
- I33M (p.Ile33Met), TOPMed rs1863827098
- I33S (p.Ile33Ser), TOPMed rs1009356572, REVEL 0.20, MetaLR 0.01
- I33V (p.Ile33Val), TOPMed rs956736880, REVEL 0.10, MetaLR 0.01
- I33I (p.Ile33Ile), rs1863827098, gnomAD 12-4274139-C-T, CADD 15.20
- E34K (p.Glu34Lys), Ensembl rs2120513661
- E34Q (p.Glu34Gln), rs2120513661, ClinGen CA383661631, ClinVar RCV002473969, AlphaMissense 1.00, MetaLR 0.21, Uncertain significance, not provided
- E35K (p.Glu35Lys), TOPMed rs1565430722, gnomAD rs1565430722, REVEL 0.31, MetaLR 0.05
- E35Q (p.Glu35Gln), TOPMed rs1565430722, gnomAD rs1565430722
- E35V (p.Glu35Val), Ensembl rs2120513697
- E35D (p.Glu35Asp), gnomAD 12-4274145-G-C, REVEL 0.18, CADD 24.10
- R36G (p.Arg36Gly), TOPMed rs1863827210
- R36H (p.Arg36His), Ensembl rs2120513730
- R36R (p.Arg36Arg), gnomAD 12-4274148-C-G, CADD 15.50
- Y37H (p.Tyr37His), ExAC rs746820501, gnomAD rs746820501, REVEL 0.20, MetaLR 0.06
- Y37Y (p.Tyr37Tyr), rs768686427, gnomAD 12-4274151-C-T, CADD 13.70
- L38R (p.Leu38Arg), rs2497479820, ClinGen CA383661663, ClinVar RCV004430722, Uncertain significance, Inborn genetic diseases
- L38L (p.Leu38Leu), rs146122734, gnomAD 12-4274154-T-C, CADD 8.81
- P39L (p.Pro39Leu), Ensembl rs2120513775
- P39P (p.Pro39Pro), rs1328275254, gnomAD 12-4274157-G-T, CADD 6.87
- Q40* (p.Gln40Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q40P (p.Gln40Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- C41G (p.Cys41Gly), TOPMed rs1215532509, gnomAD rs1215532509, REVEL 0.15, MetaLR 0.02
- C41Y (p.Cys41Tyr), Ensembl rs2120513829, Uncertain significance, not provided
- S42C (p.Ser42Cys), gnomAD rs1401047935, REVEL 0.36, MetaLR 0.08
- F44I (p.Phe44Ile), gnomAD 12-4274170-T-A, REVEL 0.33, CADD 32.00
- F44F (p.Phe44Phe), rs1863827798, gnomAD 12-4274172-C-T, CADD 15.60
- C46* (p.Cys46Ter), Ensembl rs2120513866
- C46C (p.Cys46Cys), rs2120513866, gnomAD 12-4274178-C-T, CADD 14.20
- V47L (p.Val47Leu), gnomAD rs1449067414, REVEL 0.23, MetaLR 0.07
- V47M (p.Val47Met), gnomAD rs1449067414, REVEL 0.26, MetaLR 0.10
- Q48* (p.Gln48Ter), Ensembl rs2120513895
- Q48Q (p.Gln48Gln), gnomAD 12-4274184-G-A, CADD 13.30
- K49del (p.Lys49del), gnomAD 12-4274182-CAGA-C, CADD 22.50
- K49K (p.Lys49Lys), rs1266418818, gnomAD 12-4274187-G-A, CADD 13.20
- D50D (p.Asp50Asp), rs1565430752, gnomAD 12-4274190-C-T, CADD 13.00
- I51S (p.Ile51Ser), NCI-TCGA Cosmic COSV5422, Variant assessed as somatic; moderate impact.
- I51V (p.Ile51Val), Ensembl rs1247566214
- P53H (p.Pro53His), Ensembl rs2120513942
- P53L (p.Pro53Leu), NCI-TCGA Cosmic COSV9971, REVEL 0.37, MetaLR 0.06, Uncertain significance, not provided
- P53P (p.Pro53Pro), rs761395165, gnomAD 12-4274199-C-T, CADD 13.70
- Y54T (p.Tyr54Thr), rs2120513929, gnomAD 12-4274196-AC-A, CADD 32.00
- Y54C (p.Tyr54Cys), gnomAD 12-4274201-A-G, REVEL 0.10, CADD 23.10
- M55R (p.Met55Arg), gnomAD 12-4274204-T-G, REVEL 0.52, CADD 31.00
- R56C (p.Arg56Cys), Ensembl rs2120513972
- R56H (p.Arg56His), Ensembl rs2120513983
- R56P (p.Arg56Pro), Ensembl rs2120513983
- R56R (p.Arg56Arg), gnomAD 12-4274208-C-T, CADD 15.30
- R57G (p.Arg57Gly), TOPMed rs61731957, gnomAD rs61731957, REVEL 0.33, MetaLR 0.02
- R57T (p.Arg57Thr), gnomAD rs1863828145, REVEL 0.22, MetaLR 0.03
- R57K (p.Arg57Lys), gnomAD 12-4274210-G-A, REVEL 0.18, CADD 23.70
- M58T (p.Met58Thr), ExAC rs769290616, gnomAD rs769290616, REVEL 0.33, MetaLR 0.02
- M58V (p.Met58Val), gnomAD 12-4274212-A-G, REVEL 0.27, CADD 23.10
- V59E (p.Val59Glu), Ensembl rs2120514038
- A60G (p.Ala60Gly), Ensembl rs2120514070
- A60P (p.Ala60Pro), Ensembl rs2120514058
- A60V (p.Ala60Val), Ensembl rs2120514070
- T61P (p.Thr61Pro), Ensembl rs2120514080
- T61S (p.Thr61Ser), Ensembl rs2120514080
- T61T (p.Thr61Thr), rs1863828245, gnomAD 12-4274223-C-G, CADD 14.90
- M63I (p.Met63Ile), Ensembl rs2120514105
- L64V (p.Leu64Val), Ensembl rs2120514113
- E65Q (p.Glu65Gln), gnomAD rs1234478843, REVEL 0.28, MetaLR 0.04
- E65E (p.Glu65Glu), gnomAD 12-4274235-G-A, CADD 24.00
- V66=, rs780412072, NCI-TCGA Cosmic COSV9971, Variant assessed as somatic; low impact.
- V66G (p.Val66Gly), Ensembl rs2120522358, REVEL 0.75, MetaLR 0.21
- V66F (p.Val66Phe), gnomAD 12-4276005-G-T, REVEL 0.64, CADD 34.00
- V66V (p.Val66Val), rs780412072, gnomAD 12-4276007-C-A, CADD 14.40
- C67* (p.Cys67Ter), Ensembl rs2120522400
- C67G (p.Cys67Gly), gnomAD 12-4276008-T-G, REVEL 0.53, CADD 29.70
- C67S (p.Cys67Ser), gnomAD 12-4276008-T-A, REVEL 0.38, CADD 30.00
- C67F (p.Cys67Phe), gnomAD 12-4276009-G-T, REVEL 0.68, CADD 32.00
- C67Y (p.Cys67Tyr), gnomAD 12-4276009-G-A, REVEL 0.65, CADD 32.00
- C67W (p.Cys67Trp), gnomAD 12-4276010-T-G, REVEL 0.48, CADD 24.40
- C67C (p.Cys67Cys), gnomAD 12-4276010-T-C, CADD 12.80
- E68G (p.Glu68Gly), Ensembl rs1591643829, REVEL 0.32, MetaLR 0.09
- E68K (p.Glu68Lys), gnomAD rs1349838711, REVEL 0.29, MetaLR 0.09
- E68* (p.Glu68Ter), gnomAD 12-4276011-G-T, CADD 39.00
- E68V (p.Glu68Val), gnomAD 12-4276012-A-T, REVEL 0.36, CADD 32.00
- E68A (p.Glu68Ala), gnomAD 12-4276012-A-C, REVEL 0.31, CADD 31.00
- E68D (p.Glu68Asp), gnomAD 12-4276013-G-T, REVEL 0.17, CADD 22.90
- E68E (p.Glu68Glu), rs1181684786, gnomAD 12-4276013-G-A, CADD 12.50
- E69G (p.Glu69Gly), Ensembl rs1591643835, REVEL 0.34, MetaLR 0.08
- E69K (p.Glu69Lys), gnomAD 12-4276014-G-A, REVEL 0.35, CADD 32.00
- E69E (p.Glu69Glu), gnomAD 12-4276016-A-G, CADD 11.40
- Q70* (p.Gln70Ter), Ensembl rs1591643836
- Q70K (p.Gln70Lys), Ensembl rs1591643836, REVEL 0.17, MetaLR 0.11
- Q70R (p.Gln70Arg), Ensembl rs1863869410
- K71M (p.Lys71Met), Ensembl rs2120522475
- K71R (p.Lys71Arg), gnomAD 12-4276021-A-G, REVEL 0.08, CADD 23.70
- K71K (p.Lys71Lys), gnomAD 12-4276022-G-A, CADD 14.10
- C72* (p.Cys72Ter), NCI-TCGA Cosmic COSV5422, Variant assessed as somatic; high impact.
- C72G (p.Cys72Gly), Ensembl rs2120522486
- C72S (p.Cys72Ser), Ensembl rs2120522486
- C72C (p.Cys72Cys), rs2120522500, gnomAD 12-4276025-C-T, CADD 12.20
- E73G (p.Glu73Gly), Ensembl rs2120522520
- E73K (p.Glu73Lys), Ensembl rs2120522510
Public CCND2 analysis runs
- CCND2 analysis run — CCND2 (578 variants) — completed 2026-08-19