BCR (P11274) variants and mutations
BCR (also known as P11274) is a human protein-coding gene encoding a breakpoint cluster region protein. It has serine/threonine kinase and GTPase-regulatory functions involved in cytoskeletal and signaling control. Chromosomal fusion with ABL1 creates the constitutively active BCR::ABL1 kinase that drives chronic myeloid leukemia and subsets of acute leukemia. This analysis covers 2,064 BCR variants and mutations. Of these, 90% have computational variant effect predictions. Disease context includes chronic myelogenous leukemia, BCR-ABL1 positive, acute lymphoblastic leukemia, and cancer. Example BCR variants include V2A, V2M, and V2L.
Variant analysis overview
- Gene: BCR
- Protein: P11274
- UniProt accession: P11274
- Organism: Homo sapiens
- Variants analyzed: 2064
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 1,597 unspecified-consequence records; 287 missense variants; 108 synonymous variants; 32 frameshift variants; 31 stop-gained variants; 7 in-frame deletions; 1 in-frame insertions; 1 substitution
- Prediction scores: 1,852 variants have prediction scores (90% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: chronic myelogenous leukemia, BCR-ABL1 positive, acute lymphoblastic leukemia, cancer, blast phase chronic myelogenous leukemia, BCR-ABL1 positive, neoplasm, gastrointestinal stromal tumor, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, myelodysplastic/myeloproliferative disease, myelodysplastic syndrome, leukemia, lymphoid leukemia.
Protein structure and variant hotspots
- Protein features: 4 domains; 24 post-translational modification sites.
- Structural context: 676 variants have structural context.
- PTM context: 31 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable BCR variants
Examples include V2A, V2M, V2L, V2V, D3A, D3E, D3N, D3Y. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- V2A (p.Val2Ala), gnomAD rs1457503277, REVEL 0.13, CADD 26.00
- V2M (p.Val2Met), TOPMed rs1043271505, REVEL 0.13, CADD 23.40
- V2L (p.Val2Leu), gnomAD 22-23180964-G-T, REVEL 0.09, CADD 23.10
- V2V (p.Val2Val), gnomAD 22-23180966-G-T, CADD 13.10
- D3A (p.Asp3Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D3E (p.Asp3Glu), TOPMed rs1278564233, gnomAD rs1278564233, REVEL 0.14, CADD 15.90
- D3N (p.Asp3Asn), gnomAD 22-23180967-G-A, REVEL 0.14, CADD 24.10
- D3Y (p.Asp3Tyr), gnomAD 22-23180967-G-T, REVEL 0.24, CADD 26.10
- D3G (p.Asp3Gly), gnomAD 22-23180968-A-G, REVEL 0.20, CADD 24.80
- D3D (p.Asp3Asp), rs1278564233, gnomAD 22-23180969-C-T, CADD 13.60
- P4L (p.Pro4Leu), TOPMed rs2072241399, gnomAD rs2072241399, REVEL 0.13, CADD 23.50
- P4R (p.Pro4Arg), TOPMed rs2072241399, gnomAD rs2072241399, REVEL 0.10, CADD 23.60
- P4S (p.Pro4Ser), gnomAD 22-23180970-C-T, REVEL 0.10, CADD 22.40
- P4T (p.Pro4Thr), gnomAD 22-23180970-C-A, REVEL 0.06, CADD 22.30
- P4Q (p.Pro4Gln), gnomAD 22-23180971-C-A, REVEL 0.10, CADD 24.70
- P4P (p.Pro4Pro), rs1441151163, gnomAD 22-23180972-G-A, CADD 9.04
- V5E (p.Val5Glu), cosmic curated COSV10589, TOPMed rs1408782317, REVEL 0.19, CADD 25.80
- V5L (p.Val5Leu), TOPMed rs2072241533, REVEL 0.14, CADD 22.70
- V5M (p.Val5Met), gnomAD 22-23180973-G-A, REVEL 0.27, CADD 26.20
- V5A (p.Val5Ala), gnomAD 22-23180974-T-C, REVEL 0.10, CADD 22.20
- V5V (p.Val5Val), gnomAD 22-23180975-G-A, CADD 13.40
- G6R (p.Gly6Arg), ExAC rs761634532, TOPMed rs761634532, gnomAD rs761634532, REVEL 0.46, CADD 28.20
- G6S (p.Gly6Ser), gnomAD 22-23180976-G-A, REVEL 0.35, CADD 27.90
- G6C (p.Gly6Cys), gnomAD 22-23180976-G-T, REVEL 0.51, CADD 29.20
- G6V (p.Gly6Val), gnomAD 22-23180977-G-T, REVEL 0.41, CADD 25.50
- G6D (p.Gly6Asp), gnomAD 22-23180977-G-A, REVEL 0.29, CADD 25.50
- G6G (p.Gly6Gly), gnomAD 22-23180978-C-A, CADD 14.10
- F7L (p.Phe7Leu), rs1233802398, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10000, gnomAD rs1233802398, REVEL 0.42, CADD 28.70, Variant assessed as somatic; moderate impact.
- F7I (p.Phe7Ile), gnomAD 22-23180979-T-A, REVEL 0.43, CADD 27.90
- F7S (p.Phe7Ser), gnomAD 22-23180980-T-C, REVEL 0.47, CADD 31.00
- F7F (p.Phe7Phe), gnomAD 22-23180981-C-T, CADD 14.80
- A8T (p.Ala8Thr), TOPMed rs2072241759, REVEL 0.07, CADD 23.20
- A8V (p.Ala8Val), ExAC rs767433795, gnomAD rs767433795, REVEL 0.06, CADD 16.60
- A8G (p.Ala8Gly), gnomAD 22-23180980-TCG-T, CADD 26.30
- A8S (p.Ala8Ser), gnomAD 22-23180982-G-T, REVEL 0.07, CADD 23.00
- A8E (p.Ala8Glu), gnomAD 22-23180983-C-A, REVEL 0.11, CADD 21.00
- A8A (p.Ala8Ala), gnomAD 22-23180984-G-T, CADD 12.10
- E9K (p.Glu9Lys), gnomAD rs2072241873, REVEL 0.30, CADD 25.30
- E9* (p.Glu9Ter), gnomAD 22-23180985-G-T, CADD 39.00
- E9V (p.Glu9Val), gnomAD 22-23180986-A-T, REVEL 0.43, CADD 27.80
- E9G (p.Glu9Gly), gnomAD 22-23180986-A-G, REVEL 0.39, CADD 28.70
- E9D (p.Glu9Asp), gnomAD 22-23180987-G-T, REVEL 0.19, CADD 24.50
- E9E (p.Glu9Glu), gnomAD 22-23180987-G-A, CADD 13.00
- A10V (p.Ala10Val), gnomAD rs1176399990, REVEL 0.25, CADD 25.20
- A10S (p.Ala10Ser), gnomAD 22-23180988-G-T, REVEL 0.20, CADD 24.90
- A10P (p.Ala10Pro), gnomAD 22-23180988-G-C, REVEL 0.31, CADD 25.80
- A10T (p.Ala10Thr), gnomAD 22-23180988-G-A, REVEL 0.28, CADD 25.70
- A10G (p.Ala10Gly), gnomAD 22-23180989-C-G, REVEL 0.18, CADD 25.10
- A10E (p.Ala10Glu), gnomAD 22-23180989-C-A, REVEL 0.25, CADD 23.60
- A10A (p.Ala10Ala), gnomAD 22-23180990-G-T, CADD 12.20
- W11R (p.Trp11Arg), gnomAD 22-23180991-T-C, REVEL 0.66, CADD 29.10
- W11* (p.Trp11Ter), gnomAD 22-23180992-G-A, CADD 40.00
- W11L (p.Trp11Leu), gnomAD 22-23180992-G-T, REVEL 0.57, CADD 28.60
- W11S (p.Trp11Ser), gnomAD 22-23180992-G-C, REVEL 0.60, CADD 29.50
- W11C (p.Trp11Cys), gnomAD 22-23180993-G-T, REVEL 0.65, CADD 28.30
- K12R (p.Lys12Arg), cosmic curated COSV59934, Ensembl rs2072242035, REVEL 0.04, CADD 16.30
- K12* (p.Lys12Ter), gnomAD 22-23180994-A-T, CADD 37.00
- K12E (p.Lys12Glu), gnomAD 22-23180994-A-G, REVEL 0.04, CADD 23.10
- K12M (p.Lys12Met), gnomAD 22-23180995-A-T, REVEL 0.10, CADD 24.30
- K12N (p.Lys12Asn), gnomAD 22-23180996-G-T, REVEL 0.04, CADD 22.00
- K12K (p.Lys12Lys), rs756116107, gnomAD 22-23180996-G-A, CADD 10.60
- A13E (p.Ala13Glu), 1000Genomes rs199561166, TOPMed rs199561166, REVEL 0.36, CADD 24.90, Uncertain significance
- A13G (p.Ala13Gly), 1000Genomes rs199561166, TOPMed rs199561166, REVEL 0.27, CADD 25.10, Uncertain significance, not specified
- A13S (p.Ala13Ser), Ensembl rs2146187440, REVEL 0.30, CADD 26.30
- A13V (p.Ala13Val), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10000, 1000Genomes rs199561166, TOPMed rs199561166, REVEL 0.29, CADD 25.20, Uncertain significance
- A13P (p.Ala13Pro), gnomAD 22-23180997-G-C, REVEL 0.40, CADD 27.90
- A13T (p.Ala13Thr), gnomAD 22-23180997-G-A, REVEL 0.33, CADD 27.70
- A13A (p.Ala13Ala), gnomAD 22-23180999-G-A, CADD 13.30
- Q14* (p.Gln14Ter), TOPMed rs1417369835, gnomAD rs1417369835, CADD 38.00
- Q14H (p.Gln14His), gnomAD rs1400026146, REVEL 0.20, CADD 23.60
- Q14R (p.Gln14Arg), 1000Genomes rs2146187452, REVEL 0.30, CADD 25.50
- Q14K (p.Gln14Lys), gnomAD 22-23181000-C-A, REVEL 0.20, CADD 24.60
- Q14P (p.Gln14Pro), gnomAD 22-23181001-A-C, REVEL 0.40, CADD 25.90
- Q14L (p.Gln14Leu), gnomAD 22-23181001-A-T, REVEL 0.33, CADD 26.30
- Q14Q (p.Gln14Gln), gnomAD 22-23181002-G-A, CADD 9.56
- F15L (p.Phe15Leu), 1000Genomes rs1249863953, TOPMed rs1249863953, gnomAD rs1249863953, REVEL 0.41, CADD 26.80
- F15S (p.Phe15Ser), gnomAD 22-23181004-T-C, REVEL 0.43, CADD 28.10
- F15Y (p.Phe15Tyr), gnomAD 22-23181004-T-A, REVEL 0.34, CADD 26.20
- F15F (p.Phe15Phe), rs1249863953, gnomAD 22-23181005-C-T, CADD 13.30
- P16L (p.Pro16Leu), ExAC rs765207801, TOPMed rs765207801, gnomAD rs765207801, REVEL 0.23, CADD 25.10
- P16Q (p.Pro16Gln), cosmic curated COSV10000, ExAC rs765207801, TOPMed rs765207801, gnomAD rs765207801, REVEL 0.25, CADD 25.00
- P16R (p.Pro16Arg), ExAC rs765207801, TOPMed rs765207801, gnomAD rs765207801, REVEL 0.28, CADD 25.10
- P16S (p.Pro16Ser), 1000Genomes rs2072242440, gnomAD rs2072242440, REVEL 0.06, CADD 21.70
- P16T (p.Pro16Thr), 1000Genomes rs2072242440, gnomAD rs2072242440, REVEL 0.11, CADD 22.90
- P16A (p.Pro16Ala), gnomAD 22-23181006-C-G, REVEL 0.06, CADD 19.10
- P16P (p.Pro16Pro), rs372973719, gnomAD 22-23181008-G-C, CADD 11.40
- D17E (p.Asp17Glu), ExAC rs758542346, TOPMed rs758542346, gnomAD rs758542346, REVEL 0.06, CADD 14.80, Uncertain significance, not specified
- D17Y (p.Asp17Tyr), gnomAD 22-23181009-G-T, REVEL 0.22, CADD 25.70
- D17N (p.Asp17Asn), gnomAD 22-23181009-G-A, REVEL 0.13, CADD 23.90
- D17V (p.Asp17Val), gnomAD 22-23181010-A-T, REVEL 0.20, CADD 23.60
- D17G (p.Asp17Gly), gnomAD 22-23181010-A-G, REVEL 0.09, CADD 22.60
- D17D (p.Asp17Asp), rs758542346, gnomAD 22-23181011-C-T, CADD 11.40
- S18A (p.Ser18Ala), ExAC rs777901995
- S18Q (p.Ser18Gln), gnomAD 22-23181011-CT-C, CADD 24.00
- S18P (p.Ser18Pro), gnomAD 22-23181012-T-C, REVEL 0.25, CADD 24.80
- S18* (p.Ser18Ter), gnomAD 22-23181013-C-A, CADD 36.00
- S18L (p.Ser18Leu), gnomAD 22-23181013-C-T, REVEL 0.11, CADD 23.50
- S18S (p.Ser18Ser), rs747241983, gnomAD 22-23181014-A-G, CADD 8.90
- E19A (p.Glu19Ala), TOPMed rs1235158409, gnomAD rs1235158409, REVEL 0.19, CADD 24.40
- E19Q (p.Glu19Gln), ExAC rs757563933, gnomAD rs757563933, REVEL 0.23, CADD 24.70
- E19R (p.Glu19Arg), rs749045362, gnomAD 22-23181013-C-CA, CADD 24.80
- E19* (p.Glu19Ter), gnomAD 22-23181015-G-T, CADD 37.00
- E19V (p.Glu19Val), gnomAD 22-23181016-A-T, REVEL 0.28, CADD 25.00
- E19G (p.Glu19Gly), gnomAD 22-23181016-A-G, REVEL 0.17, CADD 25.00
- E19D (p.Glu19Asp), gnomAD 22-23181017-G-T, REVEL 0.07, CADD 17.50
- E19E (p.Glu19Glu), rs781572099, gnomAD 22-23181017-G-A, CADD 9.70
- P20A (p.Pro20Ala), ExAC rs746347186, gnomAD rs746347186, REVEL 0.28, CADD 22.70
- P20L (p.Pro20Leu), gnomAD rs1216823607, REVEL 0.34, CADD 25.00
- P20T (p.Pro20Thr), ExAC rs746347186, gnomAD rs746347186, REVEL 0.32, CADD 23.90
- P20S (p.Pro20Ser), gnomAD 22-23181018-C-T, REVEL 0.33, CADD 24.20
- P20H (p.Pro20His), gnomAD 22-23181019-C-A, REVEL 0.24, CADD 24.70
- P20P (p.Pro20Pro), rs774852686, gnomAD 22-23181020-C-A, CADD 6.83
- P21Q (p.Pro21Gln), 1000Genomes rs551631242, ExAC rs551631242, TOPMed rs551631242, gnomAD rs551631242, REVEL 0.50, CADD 24.50
- P21R (p.Pro21Arg), 1000Genomes rs551631242, ExAC rs551631242, TOPMed rs551631242, gnomAD rs551631242, REVEL 0.56, CADD 24.60
- P21A (p.Pro21Ala), gnomAD 22-23181017-GCC-G, CADD 24.50
- P21T (p.Pro21Thr), gnomAD 22-23181021-C-A, REVEL 0.50, CADD 24.10
- P21S (p.Pro21Ser), gnomAD 22-23181021-C-T, REVEL 0.46, CADD 24.30
- P21L (p.Pro21Leu), gnomAD 22-23181022-C-T, REVEL 0.50, CADD 25.00
- P21P (p.Pro21Pro), gnomAD 22-23181023-G-C, CADD 11.20
- R22C (p.Arg22Cys), ExAC rs774090412, gnomAD rs774090412, REVEL 0.10, CADD 23.40
- R22H (p.Arg22His), 1000Genomes rs376532812, ESP rs376532812, ExAC rs376532812, TOPMed rs376532812, REVEL 0.09, CADD 22.60
- R22L (p.Arg22Leu), cosmic curated COSV99045, 1000Genomes rs376532812, ESP rs376532812, ExAC rs376532812, REVEL 0.06, CADD 20.10, Uncertain significance, not specified
- R22P (p.Arg22Pro), 1000Genomes rs376532812, ESP rs376532812, ExAC rs376532812, TOPMed rs376532812, REVEL 0.09, CADD 21.10
- R22A (p.Arg22Ala), gnomAD 22-23181017-G-GC, CADD 24.60
- R22S (p.Arg22Ser), gnomAD 22-23181024-C-A, REVEL 0.07, CADD 18.70
- R22G (p.Arg22Gly), gnomAD 22-23181024-C-G, REVEL 0.06, CADD 20.40
- R22R (p.Arg22Arg), gnomAD 22-23181026-C-T, CADD 10.30
- M23I (p.Met23Ile), ExAC rs773189108, gnomAD rs773189108, REVEL 0.27, CADD 24.50
- M23V (p.Met23Val), cosmic curated COSV59936, TOPMed rs1197610325, gnomAD rs1197610325, REVEL 0.21, CADD 24.00
- M23T (p.Met23Thr), gnomAD 22-23181028-T-C, REVEL 0.22, CADD 24.40
- M23R (p.Met23Arg), gnomAD 22-23181028-T-G, REVEL 0.28, CADD 25.10
- M23K (p.Met23Lys), gnomAD 22-23181028-T-A, REVEL 0.29, CADD 25.00
- E24D (p.Glu24Asp), NCI-TCGA Cosmic COSV5993, REVEL 0.06, CADD 15.40, Variant assessed as somatic; moderate impact.
- E24G (p.Glu24Gly), 1000Genomes rs571311446, ExAC rs571311446, gnomAD rs571311446, REVEL 0.13, CADD 25.30
- E24S (p.Glu24Ser), gnomAD 22-23181028-TG-T, CADD 25.30
- E24* (p.Glu24Ter), gnomAD 22-23181030-G-T, CADD 37.00
- E24E (p.Glu24Glu), rs537413302, gnomAD 22-23181032-G-A, CADD 8.25
- L25Q (p.Leu25Gln), gnomAD rs1418636261, REVEL 0.43, CADD 25.40
- L25V (p.Leu25Val), gnomAD 22-23181033-C-G, REVEL 0.31, CADD 23.60
- L25L (p.Leu25Leu), gnomAD 22-23181033-C-T, CADD 10.00
- L25M (p.Leu25Met), gnomAD 22-23181033-C-A, REVEL 0.31, CADD 23.90
- L25P (p.Leu25Pro), gnomAD 22-23181034-T-C, REVEL 0.44, CADD 25.80
- R26C (p.Arg26Cys), ExAC rs753721385, TOPMed rs753721385, gnomAD rs753721385, REVEL 0.16, CADD 23.70
- R26S (p.Arg26Ser), ExAC rs753721385, TOPMed rs753721385, gnomAD rs753721385, REVEL 0.07, CADD 16.40
- p.Arg26 Leu35del, gnomAD 22-23181028-TGGAG, CADD 19.70
- R26L (p.Arg26Leu), gnomAD 22-23181037-G-T, REVEL 0.09, CADD 20.90
- R26H (p.Arg26His), gnomAD 22-23181037-G-A, REVEL 0.11, CADD 17.80
- R26R (p.Arg26Arg), gnomAD 22-23181038-C-G, CADD 8.99
- S27A (p.Ser27Ala), Ensembl rs2072244008
- S27L (p.Ser27Leu), Ensembl rs2072244052, REVEL 0.21, CADD 22.90
- S27P (p.Ser27Pro), gnomAD 22-23181039-T-C, REVEL 0.26, CADD 24.10
- S27* (p.Ser27Ter), gnomAD 22-23181040-C-G, CADD 36.00
- S27S (p.Ser27Ser), rs758442699, gnomAD 22-23181041-A-G, CADD 10.00
- V28M (p.Val28Met), gnomAD rs1397011387, REVEL 0.05, CADD 16.60
- V28L (p.Val28Leu), gnomAD 22-23181042-G-T, REVEL 0.05, CADD 15.20
- V28G (p.Val28Gly), gnomAD 22-23181043-T-G, REVEL 0.32, CADD 24.80
- V28A (p.Val28Ala), gnomAD 22-23181043-T-C, REVEL 0.11, CADD 23.10
- V28V (p.Val28Val), rs2072244222, gnomAD 22-23181044-G-T, CADD 9.24
- G29C (p.Gly29Cys), gnomAD rs1441899010, REVEL 0.21, CADD 25.00
- G29D (p.Gly29Asp), cosmic curated COSV59934, ESP rs367800501, ExAC rs367800501, TOPMed rs367800501, REVEL 0.18, CADD 24.90
- G29A (p.Gly29Ala), gnomAD 22-23181043-TG-T, CADD 23.70
- G29S (p.Gly29Ser), gnomAD 22-23181045-G-A, REVEL 0.06, CADD 20.70
- G29V (p.Gly29Val), gnomAD 22-23181046-G-T, REVEL 0.20, CADD 23.70
- G29G (p.Gly29Gly), gnomAD 22-23181047-C-G, CADD 12.10
- D30N (p.Asp30Asn), 1000Genomes rs557214840, ExAC rs557214840, gnomAD rs557214840, REVEL 0.16, CADD 23.80
- D30Y (p.Asp30Tyr), 1000Genomes rs557214840, ExAC rs557214840, gnomAD rs557214840, REVEL 0.34, CADD 25.80
- D30H (p.Asp30His), gnomAD 22-23181048-G-C, REVEL 0.25, CADD 24.00
- D30G (p.Asp30Gly), gnomAD 22-23181049-A-G, REVEL 0.13, CADD 22.20
- D30D (p.Asp30Asp), rs757514327, gnomAD 22-23181050-C-T, CADD 11.10
- D30E (p.Asp30Glu), gnomAD 22-23181050-C-A, REVEL 0.06, CADD 18.10
- I31F (p.Ile31Phe), TOPMed rs1271305252, gnomAD rs1271305252, REVEL 0.26, CADD 24.90
- I31L (p.Ile31Leu), TOPMed rs1271305252, gnomAD rs1271305252, REVEL 0.10, CADD 23.10
- I31S (p.Ile31Ser), 1000Genomes rs2072244644, gnomAD rs2072244644, REVEL 0.30, CADD 26.80
- I31V (p.Ile31Val), TOPMed rs1271305252, gnomAD rs1271305252, REVEL 0.11, CADD 22.60, Uncertain significance, not specified
- I31T (p.Ile31Thr), gnomAD 22-23181052-T-C, REVEL 0.28, CADD 25.40
- I31I (p.Ile31Ile), gnomAD 22-23181053-C-T, CADD 13.30
- E32D (p.Glu32Asp), 1000Genomes rs144606065, ESP rs144606065, ExAC rs144606065, TOPMed rs144606065, REVEL 0.08, CADD 23.90
- E32G (p.Glu32Gly), gnomAD rs1317800552, REVEL 0.25, CADD 23.60
- E32* (p.Glu32Ter), gnomAD 22-23181054-G-T, CADD 37.00
- E32K (p.Glu32Lys), gnomAD 22-23181054-G-A, REVEL 0.22, CADD 25.30
Public BCR analysis runs
- BCR analysis run — BCR (2,064 variants) — completed 2026-08-22