PALB2 (Partner and localizer of BRCA2) variants and mutations
PALB2 (also known as Partner and localizer of BRCA2) is a human protein-coding gene encoding a partner and localizer of BRCA2 protein. It physically links BRCA1 and BRCA2 and helps recruit BRCA2-RAD51 repair machinery to DNA double-strand breaks. Heterozygous loss-of-function variants substantially increase breast and pancreatic cancer risk, while biallelic variants cause Fanconi anemia subtype N. This analysis covers 5,727 PALB2 variants and mutations. Of these, 9.6% have pathogenic or likely pathogenic clinical classifications, 58% have computational variant effect predictions from MutPred, and 27% have population-specific frequency data. Disease context includes Hereditary breast cancer, familial pancreatic carcinoma, and hereditary breast carcinoma. Example PALB2 variants include M1I, M1K, and M1L.
Variant analysis overview
- Gene: PALB2
- Protein: Partner and localizer of BRCA2
- UniProt accession: Q86YC2
- Organism: Homo sapiens
- Variants analyzed: 5727
- Variant scope: all variants
- Completed: 2026-08-09
Variant and mutation evidence
- Variant composition: 5,590 unspecified-consequence records; 20 frameshift variants; 78 synonymous variants; 22 missense variants; 3 in-frame insertions; 6 splice-region variants; 3 in-frame deletions; 1 protein altering variant; 2 substitution
- Clinical classifications: 551 pathogenic or likely pathogenic; 878 benign or likely benign; 3,228 uncertain-significance; 5 conflicting; 45 other clinical labels.
- Computational signals: 26 MutPred high-risk.
- Variant classes: 5,274 missense; 78 synonymous; 371 truncating or splice; 2 other consequence.
- Prediction scores: 3,341 variants have prediction scores (58% of the analyzed set).
- Literature: 21 publications are represented in the literature summary.
Clinical, disease, and population context
- Clinical evidence: 7 records have expert-only or criteria-backed evidence.
- Clinical annotations: 4,707 variants have clinical annotations.
- Population evidence: 1,673 variants have population-frequency evidence.
- Disease context: 25 disease associations are represented. Top associations: Hereditary breast cancer, familial pancreatic carcinoma, hereditary breast carcinoma, PALB2-related cancer predisposition, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, may be associated with breast cancer susceptibility, breast cancer patients.
Protein structure and variant hotspots
- Protein features: 8 post-translational modification sites.
- Ancestry evidence: 1,566 variants have ancestry-specific frequency data.
- PTM context: 37 variants overlap post-translational modification sites.
- 3D hotspots: 5 hotspot clusters were identified. Clusters at residues 869-1182 (tolerant, 51 variants); residues 964-1032 (tolerant, 24 variants); residues 1004-1044 (tolerant, 17 variants).
- gnomAD gene constraint: pLI 0.00 (tolerant of loss-of-function variation); LOEUF 0.76; missense Z-score 0.07.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable PALB2 variants
Examples include M1I, M1K, M1L, M1R, M1T, M1V, D2A, D2E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1057517585, ClinGen CA16042152, ClinVar RCV000410696, ClinVar RCV000505935, MetaLR 0.14, MetaSVM -0.94, Likely pathogenic, Breast-ovarian cancer, familial, susceptibility to, 5; Hereditary cancer-predisp
- M1K (p.Met1Lys), rs756519825, ClinGen CA395141289, ClinVar RCV003164576, MetaLR 0.13, MetaSVM -0.93, Uncertain significance, Hereditary cancer-predisposing syndrome
- M1L (p.Met1Leu), rs879254144, ClinGen CA395141291, ClinVar RCV002417103, MetaLR 0.13, MetaSVM -0.93, Likely pathogenic, Hereditary cancer-predisposing syndrome
- M1R (p.Met1Arg), rs756519825, ClinGen CA395141286, ClinVar RCV002435654, ClinVar RCV003102964, MetaLR 0.13, MetaSVM -0.93, Pathogenic/Likely pathogenic, Hereditary cancer-predisposing syndrome; not provided; Familial cancer of breast
- M1T (p.Met1Thr), rs756519825, ClinGen CA7963891, ClinVar RCV000230496, ClinVar RCV002436040, MetaLR 0.13, MetaSVM -0.93, Pathogenic/Likely pathogenic, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- M1V (p.Met1Val), rs879254144, ClinGen CA10584527, ClinVar RCV000237093, ClinVar RCV000696235, MetaLR 0.13, MetaSVM -0.93, Pathogenic/Likely pathogenic, Hereditary cancer-predisposing syndrome; not provided; Familial cancer of breast
- D2A (p.Asp2Ala), TOPMed rs1379618411, gnomAD rs1379618411
- D2E (p.Asp2Glu), rs1302088447, ClinGen CA395141246, ClinVar RCV003585714, TOPMed rs1302088447, AlphaMissense 0.06, MetaLR 0.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- D2G (p.Asp2Gly), rs1379618411, NCI-TCGA Cosmic COSV5516, TOPMed rs1379618411, gnomAD rs1379618411, REVEL 0.07, CADD 22.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Fanconi anemia complementation group N
- D2H (p.Asp2His), TOPMed rs1224301730, gnomAD rs1224301730, REVEL 0.07, AlphaMissense 0.32
- D2N (p.Asp2Asn), rs1224301730, ClinGen CA395141265, ClinVar RCV002343054, ClinVar RCV004572294, AlphaMissense 0.32, MetaLR 0.03, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- D2V (p.Asp2Val), TOPMed rs1379618411, gnomAD rs1379618411, MetaLR 0.02, MetaSVM -1.06
- D2Y (p.Asp2Tyr), TOPMed rs1224301730, gnomAD rs1224301730, REVEL 0.09, AlphaMissense 0.32
- E3* (p.Glu3Ter), rs878855123, ClinGen CA10583388, ClinVar RCV000231797, ClinVar RCV000582525, AlphaMissense 0.19, MetaLR 0.08, Pathogenic
- E3D (p.Glu3Asp), rs786202325, ClinGen CA194295, ClinVar RCV000165831, ClinVar RCV001036481, REVEL 0.04, CADD 13.20, Likely benign
- E3G (p.Glu3Gly), Ensembl rs2142481773
- E3K (p.Glu3Lys), rs878855123, ClinGen CA395141243, ClinVar RCV000561851, ClinVar RCV001064138, REVEL 0.10, AlphaMissense 0.19, Conflicting interpretations, Familial cancer of breast; Hereditary cancer-predisposing syndrome
- E3Q (p.Glu3Gln), rs878855123, ClinGen CA16615131, ClinVar RCV000469584, Ensembl rs878855123, AlphaMissense 0.19, MetaLR 0.08, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- E3V (p.Glu3Val), Ensembl rs2142481773, MetaLR 0.07, MetaSVM -1.06, Uncertain significance, Hereditary cancer-predisposing syndrome
- P4A (p.Pro4Ala), rs587782483, ClinGen CA395141220, ClinVar RCV003608175, TOPMed rs587782483, AlphaMissense 0.08, MetaLR 0.04, Uncertain significance, Familial cancer of breast
- P4H (p.Pro4His), ESP rs45619737, ExAC rs45619737, TOPMed rs45619737, gnomAD rs45619737, REVEL 0.04, AlphaMissense 0.36, Likely benign
- P4L (p.Pro4Leu), rs45619737, ClinGen CA288392, ClinVar RCV000114464, ClinVar RCV000116063, REVEL 0.04, CADD 15.40, Likely benign
- P4R (p.Pro4Arg), ESP rs45619737, ExAC rs45619737, TOPMed rs45619737, gnomAD rs45619737, Likely benign
- P4S (p.Pro4Ser), rs587782483, ClinGen CA294407, ClinVar RCV000131600, ClinVar RCV000205368, REVEL 0.04, AlphaMissense 0.08, Uncertain significance
- P4T (p.Pro4Thr), rs587782483, ClinGen CA395141222, ClinVar RCV000706431, TOPMed rs587782483, AlphaMissense 0.08, MetaLR 0.04, Uncertain significance, Familial cancer of breast
- P5A (p.Pro5Ala), rs377085677, ClinGen CA395141206, ClinVar RCV003500175, AlphaMissense 0.08, MetaLR 0.02, Uncertain significance, Familial cancer of breast
- P5H (p.Pro5His), Ensembl rs1967234897, Uncertain significance
- P5L (p.Pro5Leu), rs1967234897, ClinGen CA395141197, ClinVar RCV001176370, ClinVar RCV002559691, AlphaMissense 0.15, MetaLR 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- P5S (p.Pro5Ser), rs377085677, ClinGen CA269492, ClinVar RCV000114472, ClinVar RCV000116068, REVEL 0.03, AlphaMissense 0.08, Uncertain significance
- P5T (p.Pro5Thr), ESP rs377085677, ExAC rs377085677, TOPMed rs377085677, gnomAD rs377085677, REVEL 0.02, AlphaMissense 0.08, Uncertain significance
- G6A (p.Gly6Ala), gnomAD rs1388791756
- G6E (p.Gly6Glu), gnomAD rs1388791756
- G6R (p.Gly6Arg), rs1967234587, ClinGen CA395141196, ClinVar RCV001322515, ClinVar RCV005692323, AlphaMissense 0.22, MetaLR 0.05, Conflicting interpretations, Familial cancer of breast; Hereditary cancer-predisposing syndrome
- G6W (p.Gly6Trp), rs1967234587, ClinGen CA395141190, ClinVar RCV002012898, Ensembl rs1967234587, AlphaMissense 0.22, MetaLR 0.05, Uncertain significance, Familial cancer of breast
- K7E (p.Lys7Glu), Ensembl rs2142481476
- K7M (p.Lys7Met), rs947155109, ClinGen CA395141162, ClinVar RCV001317714, TOPMed rs947155109, REVEL 0.09, CADD 26.60, Uncertain significance, Familial cancer of breast
- K7N (p.Lys7Asn), rs1424944402, ClinGen CA395141157, ClinVar RCV001030102, ClinVar RCV005692273, AlphaMissense 0.55, MetaLR 0.10, Likely benign, Hereditary cancer-predisposing syndrome
- K7R (p.Lys7Arg), rs947155109, ClinGen CA16620166, ClinVar RCV000483460, ClinVar RCV000571040, REVEL 0.04, CADD 22.60, Conflicting interpretations, Familial cancer of breast; PALB2-related disorder; not specified
- P8A (p.Pro8Ala), rs2506572755, ClinGen CA2695197622, ClinVar RCV003452366, REVEL 0.04, AlphaMissense 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome
- P8L (p.Pro8Leu), rs150390726, ClinGen CA299799, ClinVar RCV000114527, ClinVar RCV000160872, REVEL 0.06, CADD 23.10, Benign
- P8S (p.Pro8Ser), rs876660586, ClinGen CA395141151, ClinVar RCV000575831, ClinVar RCV001858135, AlphaMissense 0.09, MetaLR 0.04, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- P8T (p.Pro8Thr), rs876660586, ClinGen CA395141153, ClinVar RCV000773884, ClinVar RCV001209051, REVEL 0.04, AlphaMissense 0.09, Conflicting interpretations, Breast-ovarian cancer, familial, susceptibility to, 5; Hereditary cancer-predisp
- L9F (p.Leu9Phe), rs1060502744, ClinGen CA16614884, ClinVar RCV000464168, ClinVar RCV000566603, REVEL 0.14, CADD 26.90, Uncertain significance, Familial pancreatic carcinoma; Hereditary breast ovarian cancer syndrome; Heredi
- L9H (p.Leu9His), rs515726092, ClinGen CA269558, ClinVar RCV001030104, Ensembl rs515726092, AlphaMissense 0.48, MetaLR 0.13, Likely benign
- L9P (p.Leu9Pro), rs515726092, ClinGen CA395141136, ClinVar RCV001524097, Ensembl rs515726092, AlphaMissense 0.48, MetaLR 0.13, Uncertain significance, Familial cancer of breast
- L9R (p.Leu9Arg), Ensembl rs515726092, Uncertain significance, Hereditary cancer-predisposing syndrome
- L9V (p.Leu9Val), Ensembl rs1060502744, REVEL 0.13, CADD 25.90, Uncertain significance
- S10C (p.Ser10Cys), rs2142481164, ClinGen CA395141126, ClinVar RCV002438034, Ensembl rs2142481164, AlphaMissense 0.23, MetaLR 0.12, Uncertain significance, Hereditary cancer-predisposing syndrome
- S10G (p.Ser10Gly), rs2142481164, ClinGen CA395141127, ClinVar RCV003311296, Ensembl rs2142481164, AlphaMissense 0.23, MetaLR 0.12, Uncertain significance, Hereditary cancer-predisposing syndrome
- S10I (p.Ser10Ile), Ensembl rs1555462510, REVEL 0.14, AlphaMissense 0.54, Uncertain significance
- S10N (p.Ser10Asn), rs876659643, ClinGen CA395141124, ClinVar RCV003182757, REVEL 0.17, AlphaMissense 0.54, Uncertain significance, Hereditary cancer-predisposing syndrome
- S10R (p.Ser10Arg), rs758500749, ClinGen CA7963889, ClinVar RCV002019440, ClinVar RCV003355751, REVEL 0.17, CADD 34.00, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- S10T (p.Ser10Thr), rs876659643, ClinGen CA395141123, ClinVar RCV001017898, Ensembl rs876659643, AlphaMissense 0.54, MetaLR 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome
- C11* (p.Cys11Ter), rs2142481060, ClinGen CA395141083, ClinVar RCV003450503, AlphaMissense 0.22, MetaLR 0.08, Pathogenic
- C11F (p.Cys11Phe), ExAC rs750720488, gnomAD rs750720488, Uncertain significance
- C11W (p.Cys11Trp), Ensembl rs2142481060
- C11Y (p.Cys11Tyr), rs750720488, ClinGen CA395141091, ClinVar RCV003607165, ExAC rs750720488, AlphaMissense 0.11, MetaLR 0.04, Uncertain significance, Familial cancer of breast
- E12A (p.Glu12Ala), rs876659744, ClinGen CA10580060, ClinVar RCV000213226, ClinVar RCV001204816, AlphaMissense 0.12, MetaLR 0.03, Uncertain significance
- E12D (p.Glu12Asp), rs760609798, ExAC rs760609798, TOPMed rs760609798, gnomAD rs760609798, AlphaMissense 0.29, MetaLR 0.06, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- E12G (p.Glu12Gly), Ensembl rs876659744, Uncertain significance
- E12K (p.Glu12Lys), rs765520187, ClinGen CA16614907, ClinVar RCV000456981, ClinVar RCV001020463, REVEL 0.07, AlphaMissense 0.15, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- E12Q (p.Glu12Gln), rs765520187, ClinGen CA7963887, ClinVar RCV001020465, ClinVar RCV002551827, AlphaMissense 0.15, MetaLR 0.06, Conflicting interpretations, Familial cancer of breast; Hereditary cancer-predisposing syndrome
- E12V (p.Glu12Val), Ensembl rs876659744, Uncertain significance
- E13* (p.Glu13Ter), rs373287455, ClinGen CA395141056, ClinVar RCV001178653, ClinVar RCV002555489, AlphaMissense 0.44, MetaLR 0.13, Pathogenic
- E13A (p.Glu13Ala), rs876658288, ClinGen CA395141053, ClinVar RCV000579852, Ensembl rs876658288, AlphaMissense 0.74, MetaLR 0.12, Uncertain significance, Hereditary cancer-predisposing syndrome
- E13D (p.Glu13Asp), rs876660538, ClinGen CA395141047, ClinVar RCV001369054, TOPMed rs876660538, REVEL 0.07, CADD 24.80, Uncertain significance, Familial cancer of breast
- E13G (p.Glu13Gly), rs876658288, ClinGen CA10580059, ClinVar RCV000213589, ClinVar RCV005090076, AlphaMissense 0.74, MetaLR 0.12, Uncertain significance
- E13K (p.Glu13Lys), rs373287455, ClinGen CA299802, ClinVar RCV000160873, ClinVar RCV000197594, REVEL 0.11, AlphaMissense 0.44, Pathogenic
- E13Q (p.Glu13Gln), rs373287455, ClinGen CA395141058, ClinVar RCV001021185, ClinVar RCV001209944, AlphaMissense 0.44, MetaLR 0.13, Uncertain significance, not specified; Hereditary cancer-predisposing syndrome; Familial cancer of breas
- E13V (p.Glu13Val), rs876658288, ClinGen CA395141051, ClinVar RCV001338033, Ensembl rs876658288, REVEL 0.10, AlphaMissense 0.74, Uncertain significance, Familial cancer of breast
- K14E (p.Lys14Glu), rs786202029, ClinGen CA191437, ClinVar RCV000164630, ClinVar RCV000693912, REVEL 0.11, AlphaMissense 0.07, Uncertain significance
- K14R (p.Lys14Arg), rs1555462506, ClinGen CA395141036, ClinVar RCV000550310, Ensembl rs1555462506, REVEL 0.14, CADD 32.00, Uncertain significance, Familial cancer of breast
- E15* (p.Glu15Ter), rs730881884, ClinGen CA299713, ClinVar RCV000160835, ClinVar RCV000567534, AlphaMissense 0.35, MetaLR 0.07, Pathogenic
- E15G (p.Glu15Gly), Ensembl rs1555462501, Uncertain significance
- E15K (p.Glu15Lys), rs730881884, ClinGen CA395141028, ClinVar RCV000571125, ClinVar RCV000635761, REVEL 0.05, AlphaMissense 0.35, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Familial cancer of breast
- E15Q (p.Glu15Gln), rs730881884, ClinGen CA395141025, ClinVar RCV003051771, AlphaMissense 0.35, MetaLR 0.07, Uncertain significance, Familial cancer of breast
- E15V (p.Glu15Val), rs1555462501, ClinGen CA395141018, ClinVar RCV000573021, ClinVar RCV001058727, AlphaMissense 0.47, MetaLR 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- K16E (p.Lys16Glu), rs1967230769, ClinGen CA395141009, ClinVar RCV001171433, Ensembl rs1967230769, REVEL 0.07, CADD 33.00, Benign, not specified
- K16M (p.Lys16Met), Ensembl rs1064795514, Uncertain significance
- K16R (p.Lys16Arg), rs1064795514, ClinGen CA16620165, ClinVar RCV000485171, ClinVar RCV000584562, AlphaMissense 0.14, MetaLR 0.04, Uncertain significance, not provided; Familial cancer of breast; Hereditary cancer-predisposing syndrome
- K16T (p.Lys16Thr), rs1064795514, ClinGen CA395141005, ClinVar RCV003156021, ClinVar RCV004697206, AlphaMissense 0.14, MetaLR 0.04, Likely pathogenic, Hereditary cancer-predisposing syndrome; not provided
- L17* (p.Leu17Ter), rs1567224232, ClinGen CA395140025, ClinVar RCV003607890, Ensembl rs1567224232, Pathogenic
- L17F (p.Leu17Phe), Ensembl rs2142461231, Likely benign
- L17I (p.Leu17Ile), TOPMed rs1297632902, gnomAD rs1297632902, REVEL 0.13, CADD 24.10
- K18* (p.Lys18Ter), Ensembl rs2142461206, Uncertain significance
- K18E (p.Lys18Glu), rs2142461206, ClinGen CA395140003, ClinVar RCV003322434, AlphaMissense 0.53, MetaLR 0.16, Uncertain significance, not specified
- K18M (p.Lys18Met), 1000Genomes rs138789658, ESP rs138789658, ExAC rs138789658, TOPMed rs138789658, Benign
- K18Q (p.Lys18Gln), rs2142461206, ClinGen CA395140005, ClinVar RCV001370150, Ensembl rs2142461206, AlphaMissense 0.53, MetaLR 0.16, Uncertain significance, Familial cancer of breast
- K18R (p.Lys18Arg), rs138789658, ClinGen CA161315, ClinVar RCV000114647, ClinVar RCV000121743, REVEL 0.18, CADD 25.10, Benign
- K18T (p.Lys18Thr), 1000Genomes rs138789658, ESP rs138789658, ExAC rs138789658, TOPMed rs138789658, Benign
- E19* (p.Glu19Ter), rs2142461160, ClinGen CA395139966, ClinVar RCV003450472, Ensembl rs2142461160, AlphaMissense 0.16, MetaLR 0.06, Pathogenic
- E19D (p.Glu19Asp), rs1967112979, ClinGen CA395139951, ClinVar RCV001982569, ClinVar RCV002352629, REVEL 0.10, CADD 22.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- E19G (p.Glu19Gly), rs2142461139, ClinGen CA395139957, ClinVar RCV003278573, AlphaMissense 0.47, MetaLR 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome
- E19K (p.Glu19Lys), rs2142461160, ClinGen CA395139970, ClinVar RCV004517783, Ensembl rs2142461160, AlphaMissense 0.16, MetaLR 0.06, Uncertain significance, Hereditary cancer-predisposing syndrome
- E19Q (p.Glu19Gln), Ensembl rs2142461160, Pathogenic
- E19V (p.Glu19Val), Ensembl rs2142461139
- K20* (p.Lys20Ter), rs2142461082, ClinGen CA395139930, ClinVar RCV002223100, Ensembl rs2142461082, Pathogenic
- K20I (p.Lys20Ile), rs876660327, ClinGen CA10580055, ClinVar RCV000221475, ClinVar RCV006612271, AlphaMissense 0.93, MetaLR 0.14, Uncertain significance
- K20N (p.Lys20Asn), gnomAD rs1196162944, Likely benign
- L21* (p.Leu21Ter), rs769240800, ClinGen CA7963863, ClinVar RCV000507280, ClinVar RCV000535566, CADD 36.00, Pathogenic
- L21I (p.Leu21Ile), Ensembl rs2142461023, Uncertain significance
- L21S (p.Leu21Ser), rs769240800, ClinGen CA395139891, ClinVar RCV001030112, ClinVar RCV002298850, REVEL 0.18, CADD 27.30, Uncertain significance, Familial cancer of breast
- L21V (p.Leu21Val), rs2142461023, ClinGen CA395139896, ClinVar RCV003500880, Ensembl rs2142461023, AlphaMissense 0.60, MetaLR 0.21, Uncertain significance, Familial cancer of breast
- A22E (p.Ala22Glu), Ensembl rs1967112519, Uncertain significance
- A22G (p.Ala22Gly), Ensembl rs1967112519, Uncertain significance
- A22P (p.Ala22Pro), rs1473970758, ClinGen CA395139877, ClinVar RCV001344066, ClinVar RCV002368134, AlphaMissense 0.96, MetaLR 0.13, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- A22S (p.Ala22Ser), gnomAD rs1473970758, REVEL 0.09, AlphaMissense 0.96, Uncertain significance, not provided
- A22T (p.Ala22Thr), gnomAD rs1473970758, Uncertain significance
- A22V (p.Ala22Val), rs1967112519, ClinGen CA395139867, ClinVar RCV001030113, ClinVar RCV001316104, AlphaMissense 0.47, MetaLR 0.11, Uncertain significance, Familial cancer of breast; Hereditary cancer-predisposing syndrome
- F23I (p.Phe23Ile), Ensembl rs2142460889
- F23L (p.Phe23Leu), Ensembl rs2142460849
- F23Y (p.Phe23Tyr), Ensembl rs2142460876
- L24* (p.Leu24Ter), Ensembl rs876658653, Uncertain significance
- L24F (p.Leu24Phe), rs587781986, ClinGen CA395139827, ClinVar RCV002382782, ClinVar RCV003500741, AlphaMissense 0.92, MetaLR 0.22, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- L24M (p.Leu24Met), Ensembl rs2142460828
- L24S (p.Leu24Ser), rs876658653, ClinGen CA10580054, ClinVar RCV000214682, ClinVar RCV000474579, REVEL 0.17, AlphaMissense 0.99, Uncertain significance
- L24W (p.Leu24Trp), rs876658653, ClinGen CA395139834, ClinVar RCV002370856, ClinVar RCV003098501, AlphaMissense 0.99, MetaLR 0.25, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- K25* (p.Lys25Ter), rs1248579792, ClinGen CA395139806, ClinVar RCV000772890, ClinVar RCV001030115, AlphaMissense 0.56, MetaLR 0.15, Pathogenic
- K25N (p.Lys25Asn), Ensembl rs2142460667
- K25Q (p.Lys25Gln), rs1248579792, ClinGen CA395139813, ClinVar RCV001030116, ClinVar RCV003160189, AlphaMissense 0.56, MetaLR 0.15, Uncertain significance, Familial cancer of breast; Hereditary cancer-predisposing syndrome
- K25R (p.Lys25Arg), rs1967111893, ClinGen CA395139798, ClinVar RCV001269179, Ensembl rs1967111893, AlphaMissense 0.23, MetaLR 0.07, Uncertain significance, not specified
- R26G (p.Arg26Gly), Ensembl rs2142460618
- R26M (p.Arg26Met), rs1967111702, ClinGen CA395139772, ClinVar RCV001212414, Ensembl rs1967111702, AlphaMissense 0.48, MetaLR 0.10, Uncertain significance, Familial cancer of breast
- R26S (p.Arg26Ser), rs45572434, ClinGen CA395139769, ClinVar RCV002416647, TOPMed rs45572434, AlphaMissense 0.83, MetaLR 0.09, Uncertain significance, Hereditary cancer-predisposing syndrome
- R26T (p.Arg26Thr), Ensembl rs1967111702, REVEL 0.11, AlphaMissense 0.48, Uncertain significance, Hereditary cancer-predisposing syndrome
- R26W (p.Arg26Trp), Ensembl rs2142460618, REVEL 0.10, CADD 28.60
- E27* (p.Glu27Ter), rs878855122, ClinGen CA10583387, ClinVar RCV000228882, ClinVar RCV000255635, CADD 36.00, Pathogenic
- E27G (p.Glu27Gly), rs2142460509, ClinGen CA395139757, ClinVar RCV001875053, ClinVar RCV006272460, AlphaMissense 0.83, MetaLR 0.21, Uncertain significance, not provided; Familial cancer of breast
- E27K (p.Glu27Lys), TOPMed rs878855122, gnomAD rs878855122, Pathogenic
- E27Q (p.Glu27Gln), TOPMed rs878855122, gnomAD rs878855122, Uncertain significance, Hereditary cancer-predisposing syndrome
- Y28* (p.Tyr28Ter), rs761533286, ClinGen CA395139726, ClinVar RCV001941952, ExAC rs761533286, CADD 26.00, Pathogenic
- Y28C (p.Tyr28Cys), rs515726129, ClinGen CA269654, ClinVar RCV000114666, ClinVar RCV000220533, REVEL 0.22, CADD 26.90, Benign
- Y28D (p.Tyr28Asp), Ensembl rs1060502762, Uncertain significance
- Y28F (p.Tyr28Phe), Ensembl rs515726129, Uncertain significance
- Y28H (p.Tyr28His), Ensembl rs1060502762, Uncertain significance, Familial cancer of breast; not provided
- Y28N (p.Tyr28Asn), rs1060502762, ClinGen CA16615316, ClinVar RCV000458643, ClinVar RCV000564398, AlphaMissense 0.97, MetaLR 0.23, Uncertain significance, PALB2-related cancer predisposition
- S29C (p.Ser29Cys), ExAC rs776110440, TOPMed rs776110440, gnomAD rs776110440, Likely benign
- S29G (p.Ser29Gly), rs776110440, ClinGen CA333979, ClinVar RCV000167900, ClinVar RCV000217631, REVEL 0.05, CADD 24.70, Likely benign
- S29I (p.Ser29Ile), rs1967110973, ClinGen CA395139714, ClinVar RCV002373420, Ensembl rs1967110973, AlphaMissense 0.48, MetaLR 0.08, Uncertain significance, Hereditary cancer-predisposing syndrome
- S29N (p.Ser29Asn), Ensembl rs1967110973, Uncertain significance
- S29R (p.Ser29Arg), rs2142460349, ClinGen CA395139710, ClinVar RCV002023352, ClinVar RCV002443055, AlphaMissense 0.71, MetaLR 0.10, Uncertain significance, Familial cancer of breast; not specified; Hereditary cancer-predisposing syndrom
- S29T (p.Ser29Thr), rs1967110973, ClinGen CA395139717, ClinVar RCV001030117, ClinVar RCV005394654, REVEL 0.03, AlphaMissense 0.48, Likely benign, Hereditary cancer-predisposing syndrome
- K30E (p.Lys30Glu), rs1967110881, ClinGen CA395139707, ClinVar RCV001325272, Ensembl rs1967110881, REVEL 0.08, CADD 24.10, Uncertain significance, Familial cancer of breast
- K30M (p.Lys30Met), Ensembl rs2142460316
- K30N (p.Lys30Asn), rs515726130, ClinGen CA269663, ClinVar RCV001030118, TOPMed rs515726130, AlphaMissense 0.92, MetaLR 0.14, Likely benign
- T31A (p.Thr31Ala), rs1967110664, ClinGen CA395139693, ClinVar RCV001055209, ClinVar RCV002445290, AlphaMissense 0.82, MetaLR 0.22, Uncertain significance, Familial cancer of breast; Hereditary cancer-predisposing syndrome
- T31I (p.Thr31Ile), rs1567224182, ClinGen CA395139673, ClinVar RCV000688103, Ensembl rs1567224182, AlphaMissense 0.89, MetaLR 0.23, Uncertain significance, Hereditary cancer-predisposing syndrome
- T31R (p.Thr31Arg), Ensembl rs1567224182, Uncertain significance
- T31S (p.Thr31Ser), rs1967110664, ClinGen CA395139691, ClinVar RCV003054911, Ensembl rs1967110664, AlphaMissense 0.82, MetaLR 0.22, Uncertain significance, Familial cancer of breast
- L32I (p.Leu32Ile), rs151316635, ClinGen CA395139668, ClinVar RCV001344906, ClinVar RCV004719141, REVEL 0.16, CADD 18.30, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Familial cancer of breast
- L32P (p.Leu32Pro), rs1967110180, ClinGen CA395139658, ClinVar RCV001296782, ClinVar RCV005232247, AlphaMissense 0.52, MetaLR 0.16, Uncertain significance, not specified; Familial cancer of breast
- L32Q (p.Leu32Gln), Ensembl rs1967110180, Uncertain significance
- L32R (p.Leu32Arg), Ensembl rs1967110180, Uncertain significance
- L32V (p.Leu32Val), rs151316635, ClinGen CA161318, ClinVar RCV000114673, ClinVar RCV000116117, REVEL 0.15, CADD 14.60, Likely benign
- A33D (p.Ala33Asp), rs780769645, ClinGen CA395139640, ClinVar RCV002025418, ClinVar RCV004999589, AlphaMissense 0.50, MetaLR 0.13, Uncertain significance, not provided; Familial cancer of breast
- A33G (p.Ala33Gly), ExAC rs780769645, gnomAD rs780769645, Uncertain significance
- A33P (p.Ala33Pro), rs747302288, ClinGen CA395139652, ClinVar RCV000689943, ClinVar RCV003483707, REVEL 0.18, CADD 25.10, Conflicting interpretations, Hereditary breast ovarian cancer syndrome; Familial cancer of breast
- A33S (p.Ala33Ser), ExAC rs747302288, gnomAD rs747302288, Likely benign
- A33T (p.Ala33Thr), rs747302288, ClinGen CA7963862, ClinVar RCV000580732, ClinVar RCV002530755, REVEL 0.16, CADD 25.10, Uncertain significance, Familial cancer of breast; Hereditary cancer-predisposing syndrome
- A33V (p.Ala33Val), rs780769645, ClinGen CA7963861, ClinVar RCV001359664, ExAC rs780769645, REVEL 0.17, AlphaMissense 0.50, Uncertain significance, Familial cancer of breast
- R34C (p.Arg34Cys), rs373483056, ClinGen CA191499, ClinVar RCV000164663, ClinVar RCV000199940, REVEL 0.19, CADD 28.50, Uncertain significance
- R34G (p.Arg34Gly), ESP rs373483056, ExAC rs373483056, TOPMed rs373483056, gnomAD rs373483056, Uncertain significance
- R34H (p.Arg34His), rs144944814, ClinGen CA164933, NCI-TCGA Cosmic COSV5516, ClinVar RCV000129692, REVEL 0.14, CADD 26.80, Uncertain significance
- R34L (p.Arg34Leu), rs144944814, ClinGen CA196241, ClinVar RCV000166587, ClinVar RCV000456690, REVEL 0.15, CADD 26.80, Uncertain significance
- R34P (p.Arg34Pro), 1000Genomes rs144944814, ESP rs144944814, ExAC rs144944814, TOPMed rs144944814, Uncertain significance
- R34S (p.Arg34Ser), ESP rs373483056, ExAC rs373483056, TOPMed rs373483056, gnomAD rs373483056, Uncertain significance
- L35F (p.Leu35Phe), rs2142459867, ClinGen CA395139614, ClinVar RCV003585712, Ensembl rs2142459867, AlphaMissense 0.60, MetaLR 0.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- L35H (p.Leu35His), ESP rs141047069, Uncertain significance
- L35I (p.Leu35Ile), Ensembl rs2142459867, Uncertain significance
- L35P (p.Leu35Pro), rs141047069, ClinGen CA279502031, ClinVar RCV000813912, ClinVar RCV002397684, REVEL 0.35, CADD 28.90, Uncertain significance, PALB2-related cancer predisposition
- L35V (p.Leu35Val), Ensembl rs2142459867, Uncertain significance
- Q36* (p.Gln36Ter), rs757369748, ClinGen CA16609607, ClinVar RCV000454301, ClinVar RCV000657579, AlphaMissense 0.16, MetaLR 0.14, Pathogenic
- Q36E (p.Gln36Glu), ExAC rs757369748, TOPMed rs757369748, gnomAD rs757369748, Uncertain significance, Familial cancer of breast
- Q36H (p.Gln36His), rs1567224146, ClinGen CA395139575, ClinVar RCV003607896, Ensembl rs1567224146, AlphaMissense 0.69, MetaLR 0.14, Uncertain significance, Familial cancer of breast
- Q36K (p.Gln36Lys), rs757369748, ClinGen CA7963860, ClinVar RCV001983448, ClinVar RCV002407252, REVEL 0.15, AlphaMissense 0.16, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- Q36L (p.Gln36Leu), Ensembl rs2142459764, Uncertain significance
- Q36R (p.Gln36Arg), rs2142459764, ClinGen CA395139581, ClinVar RCV004500004, ClinVar RCV005065158, AlphaMissense 0.22, MetaLR 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- R37C (p.Arg37Cys), rs200048921, ClinGen CA348301, NCI-TCGA Cosmic COSV9984, ClinVar RCV000204029, REVEL 0.28, AlphaMissense 0.66, Uncertain significance
- R37G (p.Arg37Gly), rs200048921, ClinGen CA395139489, ClinVar RCV000550350, ClinVar RCV000567015, AlphaMissense 0.66, MetaLR 0.17, Uncertain significance, Hereditary cancer-predisposing syndrome; Familial cancer of breast
- R37H (p.Arg37His), rs202194596, ClinGen CA288386, NCI-TCGA Cosmic COSV5516, ClinVar RCV000114460, REVEL 0.16, CADD 24.40, Benign
Public PALB2 analysis runs
- PALB2 analysis run — PALB2 (5,727 variants) — completed 2026-08-09