NOTCH2 (Q04721) variants and mutations
NOTCH2 (also known as Q04721) is a human protein-coding gene encoding a neurogenic locus notch homolog protein 2 protein. It directs cell-fate decisions in developing and adult tissues through ligand-triggered transcriptional signaling. Pathogenic variants cause Alagille syndrome type 2 or Hajdu-Cheney syndrome depending on the molecular mechanism, and somatic alterations occur in several malignancies. This analysis covers 5,267 NOTCH2 variants and mutations. Of these, 54% have computational variant effect predictions. Disease context includes acroosteolysis dominant type, Alagille syndrome due to a NOTCH2 point mutation, and Alagille syndrome. Example NOTCH2 variants include M1I, P2L, and P2R.
Variant analysis overview
- Gene: NOTCH2
- Protein: Q04721
- UniProt accession: Q04721
- Organism: Homo sapiens
- Variants analyzed: 5267
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 4,860 unspecified-consequence records; 1 stop retained variant; 2 stop lost; 218 synonymous variants; 9 frameshift variants; 7 in-frame deletions; 162 missense variants; 1 stop-gained variants; 2 in-frame insertions; 1 splice-region variants; 4 substitution
- Prediction scores: 2,824 variants have prediction scores (54% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acroosteolysis dominant type, Alagille syndrome due to a NOTCH2 point mutation, Alagille syndrome, diffuse large B-cell lymphoma, diabetes mellitus, cutaneous squamous cell carcinoma, keratoacanthoma, prostate adenocarcinoma, type 2 diabetes mellitus, lung carcinoma, melanoma, prostate carcinoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 35 domains; 18 post-translational modification sites.
- Structural context: 2,399 variants have structural context.
- PTM context: 40 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, ClinGen, MaveDB, LitVar.
Notable NOTCH2 variants
Examples include M1I, P2L, P2R, P2S, A3P, A3S, A3T, A3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs56159748, ClinGen CA1041068, ClinVar RCV001656212, MetaLR 0.14, MetaSVM -0.94, Benign, not provided
- P2L (p.Pro2Leu), TOPMed rs1336639565, gnomAD rs1336639565, REVEL 0.43, CADD 26.50
- P2R (p.Pro2Arg), TOPMed rs1336639565, gnomAD rs1336639565, MetaLR 0.33, MetaSVM -0.66
- P2S (p.Pro2Ser), ExAC rs782173854, gnomAD rs782173854, REVEL 0.39, CADD 25.80
- A3P (p.Ala3Pro), ExAC rs782113557, gnomAD rs782113557, Benign
- A3S (p.Ala3Ser), rs782113557, ClinGen CA249100, ClinVar RCV000202905, ClinVar RCV001640305, REVEL 0.31, CADD 22.40, Benign/Likely benign, not specified; not provided; Alagille syndrome due to a NOTCH2 point mutation
- A3T (p.Ala3Thr), ExAC rs782113557, gnomAD rs782113557, REVEL 0.34, CADD 22.90, Benign
- A3V (p.Ala3Val), rs200646249, ClinGen CA1041064, ClinVar RCV001733725, ClinVar RCV004711713, REVEL 0.32, CADD 22.50, Likely benign, Alagille syndrome due to a NOTCH2 point mutation; not provided
- L4M (p.Leu4Met), ExAC rs782725828, TOPMed rs782725828, gnomAD rs782725828, REVEL 0.23, CADD 24.00
- L4P (p.Leu4Pro), gnomAD rs1553217948, REVEL 0.39, CADD 24.80
- R5C (p.Arg5Cys), ExAC rs781919354, gnomAD rs781919354, REVEL 0.15, CADD 23.70
- R5G (p.Arg5Gly), ExAC rs781919354, gnomAD rs781919354, REVEL 0.29, CADD 21.70
- R5H (p.Arg5His), TOPMed rs1234964366, gnomAD rs1234964366, REVEL 0.25, CADD 22.00
- R5L (p.Arg5Leu), TOPMed rs1234964366, gnomAD rs1234964366, REVEL 0.25, CADD 21.50
- P6A (p.Pro6Ala), ExAC rs781993162, TOPMed rs781993162, gnomAD rs781993162, REVEL 0.25, CADD 22.80, Uncertain significance
- P6L (p.Pro6Leu), ExAC rs782374128, gnomAD rs782374128, REVEL 0.25, CADD 24.10
- P6R (p.Pro6Arg), ExAC rs782374128, gnomAD rs782374128, REVEL 0.32, CADD 22.80
- P6S (p.Pro6Ser), rs781993162, ClinGen CA1041059, ClinVar RCV004488225, ExAC rs781993162, REVEL 0.28, CADD 23.10, Uncertain significance, Inborn genetic diseases
- A7G (p.Ala7Gly), TOPMed rs1553217938, gnomAD rs1553217938, REVEL 0.18, CADD 19.20
- A7P (p.Ala7Pro), NCI-TCGA Cosmic COSV5668, NCI-TCGA Cosmic COSV5669, Ensembl rs2101452527, Variant assessed as somatic; moderate impact.
- A7S (p.Ala7Ser), rs2101452527, ClinGen CA341853324, ClinVar RCV004547300, REVEL 0.12, CADD 16.60, Uncertain significance, Alagille syndrome due to a NOTCH2 point mutation
- L9M (p.Leu9Met), gnomAD rs1553217934, REVEL 0.37, CADD 22.80
- L9P (p.Leu9Pro), TOPMed rs1655666889, REVEL 0.57, CADD 23.00
- W10* (p.Trp10Ter), rs782598895, ClinGen CA1041056, ClinVar RCV001849581, ExAC rs782598895, CADD 36.00, Pathogenic
- W10C (p.Trp10Cys), NCI-TCGA TCGA novel, REVEL 0.20, CADD 23.10, Variant assessed as somatic; moderate impact.
- W10G (p.Trp10Gly), gnomAD rs1553217930, REVEL 0.28, CADD 22.20, Uncertain significance
- W10R (p.Trp10Arg), rs1553217930, ClinGen CA341853306, ClinVar RCV002924426, gnomAD rs1553217930, REVEL 0.17, CADD 21.50, Uncertain significance, Inborn genetic diseases
- A11E (p.Ala11Glu), ExAC rs782442735, TOPMed rs782442735, gnomAD rs782442735, REVEL 0.44, CADD 16.60
- A11S (p.Ala11Ser), TOPMed rs1231551231, gnomAD rs1231551231, REVEL 0.20, CADD 17.40
- A11T (p.Ala11Thr), TOPMed rs1231551231, gnomAD rs1231551231, REVEL 0.19, CADD 19.70
- A11V (p.Ala11Val), ExAC rs782442735, TOPMed rs782442735, gnomAD rs782442735, REVEL 0.17, CADD 20.70, Uncertain significance, Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome
- L12P (p.Leu12Pro), Ensembl rs2101452403
- L12V (p.Leu12Val), gnomAD rs1553217927, REVEL 0.31, CADD 23.10
- A14E (p.Ala14Glu), 1000Genomes rs587662181, ExAC rs587662181, TOPMed rs587662181, gnomAD rs587662181, REVEL 0.43, CADD 16.70
- A14G (p.Ala14Gly), 1000Genomes rs587662181, ExAC rs587662181, TOPMed rs587662181, gnomAD rs587662181, REVEL 0.21, CADD 20.30
- A14V (p.Ala14Val), 1000Genomes rs587662181, ExAC rs587662181, TOPMed rs587662181, gnomAD rs587662181, REVEL 0.13, CADD 20.60
- L15F (p.Leu15Phe), Ensembl rs1570805519, REVEL 0.38, CADD 22.20
- L15H (p.Leu15His), Ensembl rs2101452349
- L15R (p.Leu15Arg), Ensembl rs2101452349
- W16* (p.Trp16Ter), gnomAD rs1553217924, CADD 35.00
- L17M (p.Leu17Met), gnomAD rs1553217920, REVEL 0.23, CADD 20.30
- L17V (p.Leu17Val), gnomAD rs1553217920, REVEL 0.16, CADD 18.00
- C18R (p.Cys18Arg), gnomAD rs1553217919, REVEL 0.19, CADD 17.00
- C18W (p.Cys18Trp), ExAC rs782697240, TOPMed rs782697240, gnomAD rs782697240, MetaLR 0.04, MetaSVM -1.06
- C18Y (p.Cys18Tyr), ExAC rs781804379, gnomAD rs781804379, REVEL 0.15, CADD 16.30
- C19F (p.Cys19Phe), ExAC rs782166299, gnomAD rs782166299, REVEL 0.07, CADD 16.80
- C19W (p.Cys19Trp), rs11810554, ClinGen CA1041044, ClinVar RCV000986405, ClinVar RCV001700685, REVEL 0.10, CADD 21.70, Benign, not specified; not provided; Hajdu-Cheney syndrome
- C19Y (p.Cys19Tyr), ExAC rs782166299, gnomAD rs782166299, REVEL 0.10, CADD 16.30
- A20E (p.Ala20Glu), TOPMed rs1302570383, gnomAD rs1302570383, REVEL 0.35, CADD 17.10
- A20G (p.Ala20Gly), TOPMed rs1302570383, gnomAD rs1302570383, REVEL 0.15, CADD 17.30
- A20P (p.Ala20Pro), gnomAD rs1553217914, REVEL 0.26, CADD 17.60
- A20S (p.Ala20Ser), gnomAD rs1553217914, REVEL 0.08, CADD 15.40
- A20V (p.Ala20Val), TOPMed rs1302570383, gnomAD rs1302570383, REVEL 0.17, CADD 16.40
- A21D (p.Ala21Asp), ExAC rs782179651, TOPMed rs782179651, gnomAD rs782179651, REVEL 0.15, CADD 10.80
- A21G (p.Ala21Gly), ExAC rs782179651, TOPMed rs782179651, gnomAD rs782179651, REVEL 0.13, CADD 11.20
- A21S (p.Ala21Ser), 1000Genomes rs2603926, ExAC rs2603926, TOPMed rs2603926, gnomAD rs2603926, REVEL 0.05, CADD 14.00, Benign
- A21T (p.Ala21Thr), rs2603926, ClinGen CA1041041, ClinVar RCV001641019, ClinVar RCV001699827, REVEL 0.05, CADD 16.20, Benign, not specified; not provided
- A21V (p.Ala21Val), ExAC rs782179651, TOPMed rs782179651, gnomAD rs782179651, REVEL 0.07, CADD 12.60, Likely benign, Inborn genetic diseases
- P22A (p.Pro22Ala), TOPMed rs868921483, gnomAD rs868921483, REVEL 0.05, CADD 13.80
- P22H (p.Pro22His), ExAC rs782038396, TOPMed rs782038396, gnomAD rs782038396, REVEL 0.13, CADD 18.20
- P22L (p.Pro22Leu), ExAC rs782038396, TOPMed rs782038396, gnomAD rs782038396, REVEL 0.06, CADD 17.40
- P22S (p.Pro22Ser), TOPMed rs868921483, gnomAD rs868921483, REVEL 0.04, CADD 15.60
- A23E (p.Ala23Glu), ExAC rs782502909, gnomAD rs782502909, REVEL 0.20, CADD 18.10
- A23G (p.Ala23Gly), ExAC rs782502909, gnomAD rs782502909, MetaLR 0.04, MetaSVM -1.06
- A23S (p.Ala23Ser), ExAC rs782643034, REVEL 0.10, CADD 15.60
- A23V (p.Ala23Val), ExAC rs782502909, gnomAD rs782502909, REVEL 0.12, CADD 18.70
- H24L (p.His24Leu), gnomAD rs1553217905, REVEL 0.08, CADD 7.52
- H24Q (p.His24Gln), gnomAD rs1553217903, REVEL 0.04, CADD 4.64
- H24R (p.His24Arg), gnomAD rs1553217905, MetaLR 0.01, MetaSVM -0.96
- A25E (p.Ala25Glu), gnomAD rs1553210734
- A25P (p.Ala25Pro), ExAC rs782589993, gnomAD rs782589993
- A25T (p.Ala25Thr), ExAC rs782589993, gnomAD rs782589993, REVEL 0.24, CADD 27.00
- A25V (p.Ala25Val), gnomAD rs1553210734, REVEL 0.24, CADD 25.70
- Q27* (p.Gln27Ter), gnomAD rs1553210729
- Q27P (p.Gln27Pro), TOPMed rs1654028509
- R29* (p.Arg29Ter), rs1174406807, ClinGen CA341849570, ClinVar RCV000986404, ClinVar RCV001312091, CADD 36.00, Likely pathogenic
- R29Q (p.Arg29Gln), TOPMed rs1654028328, REVEL 0.09, CADD 22.00
- D30G (p.Asp30Gly), gnomAD rs1553210725, REVEL 0.19, CADD 19.70
- G31D (p.Gly31Asp), Ensembl rs1654028127, REVEL 0.13, CADD 11.10
- Y32C (p.Tyr32Cys), ExAC rs782447884, TOPMed rs782447884, gnomAD rs782447884, REVEL 0.17, CADD 22.30
- P34H (p.Pro34His), gnomAD rs1553210721, REVEL 0.71, CADD 25.20
- P34R (p.Pro34Arg), gnomAD rs1553210721, REVEL 0.74, CADD 25.20
- C35* (p.Cys35Ter), gnomAD rs1553210720
- C35R (p.Cys35Arg), ExAC rs781887969, REVEL 0.90, CADD 27.20
- C35Y (p.Cys35Tyr), gnomAD rs1654027638, REVEL 0.92, CADD 25.90
- N37D (p.Asn37Asp), TOPMed rs1553210719, gnomAD rs1553210719, MetaLR 0.49, MetaSVM -0.13
- N37S (p.Asn37Ser), ExAC rs782653854, gnomAD rs782653854, REVEL 0.55, CADD 25.60
- E38G (p.Glu38Gly), 1000Genomes rs587603038, REVEL 0.11, CADD 19.30
- E38K (p.Glu38Lys), rs61788901, ClinGen CA1040937, ClinVar RCV001528862, ClinVar RCV004714258, REVEL 0.07, CADD 20.70, Benign, not specified; not provided
- G39E (p.Gly39Glu), gnomAD rs1553210717, REVEL 0.86, CADD 25.50
- M40R (p.Met40Arg), Ensembl rs1654026770
- M40V (p.Met40Val), cosmic curated COSV56707, gnomAD rs1311357227, MetaLR 0.03, MetaSVM -1.00
- C41Y (p.Cys41Tyr), gnomAD rs1553210714, MetaLR 0.98, MetaSVM 1.03
- V42I (p.Val42Ile), ExAC rs782736063, gnomAD rs782736063, REVEL 0.16, CADD 14.80
- H45L (p.His45Leu), cosmic curated COSV56710, gnomAD rs1410246337
- H45N (p.His45Asn), Ensembl rs879972657, MetaLR 0.04, MetaSVM -1.02
- H45P (p.His45Pro), gnomAD rs1410246337, REVEL 0.18, CADD 23.00
- N46H (p.Asn46His), gnomAD rs1553210709, REVEL 0.27, CADD 26.00
- N46I (p.Asn46Ile), ExAC rs61788900, gnomAD rs61788900, MetaLR 0.30, MetaSVM -0.50, Benign
- N46S (p.Asn46Ser), rs61788900, ClinGen CA1040934, cosmic curated COSV56680, ClinVar RCV000986403, REVEL 0.10, CADD 23.70, Benign, not specified; not provided; Hajdu-Cheney syndrome
- G47S (p.Gly47Ser), gnomAD rs1553210707
- T48A (p.Thr48Ala), gnomAD rs1553210706
- G49E (p.Gly49Glu), cosmic curated COSV56687, Ensembl rs2101329636
- Y50H (p.Tyr50His), TOPMed rs1654025449, gnomAD rs1654025449, REVEL 0.13, CADD 23.90
- C51* (p.Cys51Ter), Ensembl rs2101329597, CADD 36.00
- C51R (p.Cys51Arg), NCI-TCGA Cosmic COSV9986, cosmic curated COSV99863, Variant assessed as somatic; moderate impact.
- C51Y (p.Cys51Tyr), cosmic curated COSV99865, gnomAD rs1553210705, MetaLR 0.99, MetaSVM 0.97
- C53S (p.Cys53Ser), Ensembl rs2101243260
- P54A (p.Pro54Ala), ExAC rs782474556, TOPMed rs782474556, gnomAD rs782474556, REVEL 0.12, CADD 15.10, Likely benign, Inborn genetic diseases
- P54L (p.Pro54Leu), rs781815362, ClinGen CA1040918, ClinVar RCV002689582, ExAC rs781815362, REVEL 0.13, CADD 22.70, Uncertain significance, Inborn genetic diseases
- G56A (p.Gly56Ala), ExAC rs782568319, TOPMed rs782568319, gnomAD rs782568319, REVEL 0.60, CADD 22.30
- G56D (p.Gly56Asp), ExAC rs782568319, TOPMed rs782568319, gnomAD rs782568319, REVEL 0.72, CADD 23.10
- G56V (p.Gly56Val), ExAC rs782568319, TOPMed rs782568319, gnomAD rs782568319, MetaLR 0.77, MetaSVM 0.74
- L58* (p.Leu58Ter), NCI-TCGA Cosmic COSV9986, cosmic curated COSV99865, Variant assessed as somatic; high impact.
- L58S (p.Leu58Ser), ExAC rs782787639, gnomAD rs782787639, REVEL 0.47, CADD 25.40
- G59W (p.Gly59Trp), Ensembl rs2101243168
- E60* (p.Glu60Ter), cosmic curated COSV56694, gnomAD rs1553206175, CADD 34.00
- E60K (p.Glu60Lys), gnomAD rs1553206175, REVEL 0.29, CADD 22.90
- E60V (p.Glu60Val), Ensembl rs1652940155, REVEL 0.49, CADD 23.80, Uncertain significance, Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome
- C62S (p.Cys62Ser), Ensembl rs2101243107
- R65* (p.Arg65Ter), cosmic curated COSV10584, gnomAD rs1280158106, CADD 35.00
- R65G (p.Arg65Gly), gnomAD rs1280158106, REVEL 0.07, CADD 23.70, Uncertain significance, Inborn genetic diseases
- R65P (p.Arg65Pro), ESP rs377214276, ExAC rs377214276, TOPMed rs377214276, gnomAD rs377214276, MetaLR 0.01, MetaSVM -0.92
- R65Q (p.Arg65Gln), cosmic curated COSV56711, ESP rs377214276, ExAC rs377214276, TOPMed rs377214276, REVEL 0.04, CADD 23.00
- D66A (p.Asp66Ala), ExAC rs782066986, gnomAD rs782066986, REVEL 0.69, CADD 26.60
- D66E (p.Asp66Glu), rs1483822331, ClinGen CA341849300, ClinVar RCV003365126, TOPMed rs1483822331, REVEL 0.52, CADD 23.60, Uncertain significance, Inborn genetic diseases
- D66G (p.Asp66Gly), ExAC rs782066986, gnomAD rs782066986, MetaLR 0.51, MetaSVM 0.12
- D66H (p.Asp66His), TOPMed rs1652939327, REVEL 0.64, CADD 24.30, Uncertain significance
- D66N (p.Asp66Asn), rs1652939327, ClinGen CA341849305, ClinVar RCV002822064, TOPMed rs1652939327, REVEL 0.27, CADD 21.90, Uncertain significance, Inborn genetic diseases
- P67H (p.Pro67His), ExAC rs781921948, gnomAD rs781921948, REVEL 0.70, CADD 26.50
- P67R (p.Pro67Arg), ExAC rs781921948, gnomAD rs781921948, REVEL 0.79, CADD 26.50
- C68Y (p.Cys68Tyr), rs782412559, ClinGen CA1040908, ClinVar RCV003406731, ExAC rs782412559, AlphaMissense 0.99, MetaLR 1.00, Uncertain significance, not provided
- R72C (p.Arg72Cys), ExAC rs782131599, TOPMed rs782131599, gnomAD rs782131599, REVEL 0.28, CADD 25.10, Uncertain significance, Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome
- R72G (p.Arg72Gly), ExAC rs782131599, TOPMed rs782131599, gnomAD rs782131599, Uncertain significance
- R72H (p.Arg72His), rs201838650, ClinGen CA1040904, cosmic curated COSV99864, ClinVar RCV000435654, REVEL 0.09, CADD 22.50, Likely benign, not specified
- R72P (p.Arg72Pro), 1000Genomes rs201838650, ESP rs201838650, ExAC rs201838650, TOPMed rs201838650, MetaLR 0.02, MetaSVM -0.91, Likely benign
- R72S (p.Arg72Ser), ExAC rs782131599, TOPMed rs782131599, gnomAD rs782131599, REVEL 0.16, CADD 23.80, Uncertain significance
- Q74R (p.Gln74Arg), ExAC rs782359787, TOPMed rs782359787, gnomAD rs782359787, REVEL 0.18, CADD 22.70
- G76S (p.Gly76Ser), TOPMed rs1373951384, REVEL 0.69, CADD 25.90
- G76V (p.Gly76Val), TOPMed rs1431793217, MetaLR 0.79, MetaSVM 0.83
- T78I (p.Thr78Ile), Ensembl rs2101242909, REVEL 0.28, CADD 24.60
- T78S (p.Thr78Ser), Ensembl rs2101242909, MetaLR 0.18, MetaSVM -0.93
- A81S (p.Ala81Ser), TOPMed rs1308427063, gnomAD rs1308427063, MetaLR 0.20, MetaSVM -0.80
- A81T (p.Ala81Thr), TOPMed rs1308427063, gnomAD rs1308427063, REVEL 0.14, CADD 18.80
- A81V (p.Ala81Val), cosmic curated COSV10456, gnomAD rs1553206159, REVEL 0.17, CADD 22.50
- Q82H (p.Gln82His), NCI-TCGA Cosmic COSV5670, cosmic curated COSV56708, REVEL 0.13, CADD 19.40, Variant assessed as somatic; moderate impact.
- A83S (p.Ala83Ser), ExAC rs782209743, gnomAD rs782209743, REVEL 0.15, CADD 19.10
- A83V (p.Ala83Val), NCI-TCGA TCGA novel, Ensembl rs2101242868, MetaLR 0.02, MetaSVM -0.97, Variant assessed as somatic; moderate impact.
- M84I (p.Met84Ile), gnomAD rs1439968793, REVEL 0.20, CADD 21.00
- M84R (p.Met84Arg), TOPMed rs1353659503, REVEL 0.51, CADD 21.80, Uncertain significance, Inborn genetic diseases
- M84T (p.Met84Thr), TOPMed rs1353659503, REVEL 0.26, CADD 19.80
- M84V (p.Met84Val), 1000Genomes rs587750639, ExAC rs587750639, TOPMed rs587750639, gnomAD rs587750639, REVEL 0.27, CADD 19.00
- L85Q (p.Leu85Gln), Ensembl rs1557843126, REVEL 0.20, CADD 22.70
- G86E (p.Gly86Glu), cosmic curated COSV56690, gnomAD rs1553206150
- G86R (p.Gly86Arg), Ensembl rs1652936810
- A88D (p.Ala88Asp), gnomAD rs1553206149, REVEL 0.82, CADD 23.70
- A88V (p.Ala88Val), gnomAD rs1553206149, MetaLR 0.73, MetaSVM 0.57
- T89M (p.Thr89Met), cosmic curated COSV56706, ESP rs138537504, ExAC rs138537504, TOPMed rs138537504, REVEL 0.25, CADD 22.90, Likely benign, not provided
- T89R (p.Thr89Arg), ESP rs138537504, ExAC rs138537504, TOPMed rs138537504, gnomAD rs138537504
- T89S (p.Thr89Ser), Ensembl rs2101242800, MetaLR 0.16, MetaSVM -0.90
- C90R (p.Cys90Arg), Ensembl rs1232996741, REVEL 0.96, CADD 27.10
- R91* (p.Arg91Ter), NCI-TCGA Cosmic COSV9986, cosmic curated COSV99865, Ensembl rs2101242758, CADD 35.00, Variant assessed as somatic; high impact.
- R91L (p.Arg91Leu), rs143195893, ClinGen CA1040896, cosmic curated COSV56693, ClinVar RCV000986402, REVEL 0.14, CADD 22.10, Benign/Likely benign, Hajdu-Cheney syndrome; not provided
- R91Q (p.Arg91Gln), 1000Genomes rs143195893, ESP rs143195893, ExAC rs143195893, TOPMed rs143195893, REVEL 0.10, CADD 21.60, Uncertain significance, Alagille syndrome due to a NOTCH2 point mutation; Hajdu-Cheney syndrome
- C92R (p.Cys92Arg), TOPMed rs1652935820, gnomAD rs1652935820, REVEL 0.93, CADD 27.00
- A93V (p.Ala93Val), rs368671802, ESP rs368671802, TOPMed rs368671802, REVEL 0.21, CADD 23.90, Variant assessed as somatic; moderate impact.
- S94L (p.Ser94Leu), NCI-TCGA TCGA novel, Ensembl rs2101242712, MetaLR 0.08, MetaSVM -0.99, Variant assessed as somatic; moderate impact.
- G95A (p.Gly95Ala), ExAC rs782475359, TOPMed rs782475359, gnomAD rs782475359, REVEL 0.82, CADD 24.60
- G95E (p.Gly95Glu), ExAC rs782475359, TOPMed rs782475359, gnomAD rs782475359, REVEL 0.89, CADD 25.10
- G95W (p.Gly95Trp), Ensembl rs2101242694
- T97I (p.Thr97Ile), ExAC rs782699704, gnomAD rs782699704, REVEL 0.41, CADD 23.00
- T97R (p.Thr97Arg), ExAC rs782699704, gnomAD rs782699704, MetaLR 0.35, MetaSVM -0.31
- G98R (p.Gly98Arg), Ensembl rs1652934931
- E99A (p.Glu99Ala), gnomAD rs1553206136, REVEL 0.11, CADD 23.30
- E99D (p.Glu99Asp), Ensembl rs797037146
- E99Q (p.Glu99Gln), Ensembl rs2101242630, MetaLR 0.00, MetaSVM -0.91
- D100A (p.Asp100Ala), Ensembl rs1570738713
- D100G (p.Asp100Gly), Ensembl rs1570738713
- D100H (p.Asp100His), rs2101242610, ClinGen CA341849083, ClinVar RCV004488227, Ensembl rs2101242610, AlphaMissense 0.18, MetaLR 0.10, Uncertain significance, Inborn genetic diseases
- D100V (p.Asp100Val), Ensembl rs1570738713, MetaLR 0.18, MetaSVM -0.88
Public NOTCH2 analysis runs
- NOTCH2 analysis run — NOTCH2 (5,267 variants) — completed 2026-08-19