PMS2 (P54278) variants and mutations
PMS2 (also known as P54278) is a human protein-coding gene encoding a mismatch repair endonuclease protein. Together with MLH1, it provides endonuclease activity needed to complete DNA mismatch repair after replication errors are recognized. Germline loss-of-function variants cause Lynch syndrome, while biallelic variants cause constitutional mismatch-repair deficiency. This analysis covers 4,022 PMS2 variants and mutations. Of these, 66% have computational variant effect predictions. Disease context includes Lynch syndrome, Constitutional mismatch repair deficiency syndrome, and mismatch repair cancer syndrome 1. Example PMS2 variants include M1?, M1I, and M1K.
Variant analysis overview
- Gene: PMS2
- Protein: P54278
- UniProt accession: P54278
- Organism: Homo sapiens
- Variants analyzed: 4022
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 3,846 unspecified-consequence records; 1 stop retained variant; 100 synonymous variants; 49 missense variants; 14 frameshift variants; 2 in-frame deletions; 2 stop-gained variants; 3 splice-region variants; 5 substitution
- Prediction scores: 2,653 variants have prediction scores (66% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Lynch syndrome, Constitutional mismatch repair deficiency syndrome, mismatch repair cancer syndrome 1, endometrial carcinoma, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, hereditary nonpolyposis colon cancer, Non-polyposis Turcot syndrome, hereditary nonpolyposis colorectal carcinoma, mismatch repair cancer syndrome, Hereditary breast and ovarian cancer syndrome, breast cancer.
Protein structure and variant hotspots
- Protein features: 5 binding sites; 2 post-translational modification sites.
- PTM context: 8 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, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable PMS2 variants
Examples include M1?, M1I, M1K, M1L, M1R, M1T, M1V, E2*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, rs1554309086, ClinGen CA366745251, ClinVar RCV000519055, ClinVar RCV000535555, MetaLR 0.44, MetaSVM -0.49, Pathogenic
- M1I (p.Met1Ile), rs1554309086, ClinGen CA366745249, ClinVar RCV001950104, ClinVar RCV003452184, MetaLR 0.44, MetaSVM -0.49, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- M1K (p.Met1Lys), rs587780059, ClinGen CA011803, ClinVar RCV000160895, ClinVar RCV000212834, MetaLR 0.64, MetaSVM 0.01, Uncertain significance, Hereditary nonpolyposis colon cancer; Hereditary nonpolyposis colorectal neoplas
- M1L (p.Met1Leu), rs587779333, ClinGen CA010652, ClinVar RCV000132181, ClinVar RCV000218553, MetaLR 0.47, MetaSVM -0.58, Benign, Hereditary nonpolyposis colorectal neoplasms; Hereditary nonpolyposis colon canc
- M1R (p.Met1Arg), rs587780059, ClinGen CA10578738, ClinVar RCV000219633, ClinVar RCV000458145, MetaLR 0.64, MetaSVM 0.01, Uncertain significance, not provided; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-pr
- M1T (p.Met1Thr), rs587780059, ClinGen CA011813, ClinVar RCV000115692, ClinVar RCV000461697, MetaLR 0.64, MetaSVM 0.01, Uncertain significance, Hereditary cancer-predisposing syndrome
- M1V (p.Met1Val), rs587779333, ClinGen CA010642, ClinVar RCV000076838, ClinVar RCV000144649, MetaLR 0.47, MetaSVM -0.58, Uncertain significance, Hereditary cancer-predisposing syndrome; Lynch syndrome 4; Hereditary nonpolypos
- E2* (p.Glu2Ter), rs1554309080, ClinGen CA366745246, cosmic curated COSV99764, ClinVar RCV001958693, CADD 52.00, Pathogenic
- E2A (p.Glu2Ala), gnomAD rs876658233, Likely benign
- E2D (p.Glu2Asp), rs774177383, ClinGen CA050969, ClinVar RCV003293463, ExAC rs774177383, REVEL 0.48, CADD 15.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- E2G (p.Glu2Gly), rs876658233, ClinGen CA10578737, ClinVar RCV000219403, ClinVar RCV000557539, REVEL 0.47, AlphaMissense 0.11, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Breast and/or ovarian cancer; Here
- E2K (p.Glu2Lys), Ensembl rs1554309080, REVEL 0.50, CADD 26.70, Pathogenic
- E2Q (p.Glu2Gln), rs1554309080, ClinGen CA366745248, ClinVar RCV000543235, ClinVar RCV002341258, REVEL 0.41, CADD 24.20, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- E2V (p.Glu2Val), rs876658233, ClinGen CA366745244, ClinVar RCV000573402, ClinVar RCV004000895, AlphaMissense 0.11, MetaLR 0.75, Uncertain significance, Lynch syndrome; Hereditary cancer-predisposing syndrome
- R3* (p.Arg3Ter), rs763939668, ClinGen CA10577360, NCI-TCGA Cosmic COSV5615, cosmic curated COSV56152, CADD 39.00, Pathogenic
- R3G (p.Arg3Gly), rs763939668, ClinGen CA051682, ClinVar RCV002968140, ClinVar RCV004065108, REVEL 0.36, CADD 22.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- R3L (p.Arg3Leu), rs375507981, ClinGen CA052196, ClinVar RCV000696078, ClinVar RCV001177038, REVEL 0.36, CADD 5.32, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R3P (p.Arg3Pro), rs375507981, ClinGen CA052186, cosmic curated COSV56150, ClinVar RCV000562027, REVEL 0.45, CADD 0.21, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R3Q (p.Arg3Gln), rs375507981, ClinGen CA052177, NCI-TCGA Cosmic COSV5615, cosmic curated COSV56150, REVEL 0.38, CADD 0.16, Uncertain significance, Mismatch repair cancer syndrome 4; Lynch syndrome 4; Hereditary nonpolyposis col
- A4D (p.Ala4Asp), rs745361721, ClinGen CA366745238, ClinVar RCV001805349, ExAC rs745361721, AlphaMissense 0.12, MetaLR 0.43, Uncertain significance, Hereditary cancer-predisposing syndrome
- A4G (p.Ala4Gly), rs745361721, ClinGen CA042517, ClinVar RCV000214339, ClinVar RCV000222258, REVEL 0.48, AlphaMissense 0.12, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- A4P (p.Ala4Pro), rs1786257764, ClinGen CA366745241, ClinVar RCV001223801, ClinVar RCV004570541, AlphaMissense 0.10, MetaLR 0.38, Uncertain significance, Hereditary cancer-predisposing syndrome; Lynch syndrome 4; Hereditary nonpolypos
- A4S (p.Ala4Ser), rs1786257764, ClinGen CA366745240, ClinVar RCV003045363, Ensembl rs1786257764, AlphaMissense 0.10, MetaLR 0.38, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- A4T (p.Ala4Thr), rs1786257764, ClinGen CA366745242, ClinVar RCV002430956, ClinVar RCV003759743, AlphaMissense 0.10, MetaLR 0.38, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- A4V (p.Ala4Val), rs745361721, ClinGen CA366745239, ClinVar RCV000570482, ClinVar RCV001301831, REVEL 0.52, AlphaMissense 0.12, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- E5* (p.Glu5Ter), rs1282857832, ClinGen CA840354122, ClinVar RCV001918193, AlphaMissense 0.17, MetaLR 0.60, Pathogenic
- E5G (p.Glu5Gly), rs876659080, ClinGen CA366745234, ClinVar RCV001064928, ClinVar RCV002393315, AlphaMissense 0.06, MetaLR 0.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- E5K (p.Glu5Lys), rs372539944, ClinGen CA366745237, NCI-TCGA Cosmic COSV5614, cosmic curated COSV56149, AlphaMissense 0.17, MetaLR 0.60, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- E5Q (p.Glu5Gln), rs372539944, ClinGen CA043392, NCI-TCGA Cosmic COSV5614, cosmic curated COSV56152, REVEL 0.33, AlphaMissense 0.17, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; not specified; Hereditary cancer-p
- E5V (p.Glu5Val), rs876659080, ClinGen CA10578735, ClinVar RCV000214871, ClinVar RCV000685125, REVEL 0.50, AlphaMissense 0.06, Uncertain significance, not provided; Lynch syndrome; Lynch syndrome 4
- S6C (p.Ser6Cys), rs1786254768, ClinGen CA366745229, ClinVar RCV001319773, ClinVar RCV003365328, AlphaMissense 0.06, MetaLR 0.58, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- S6G (p.Ser6Gly), Ensembl rs1786254768, Uncertain significance
- S6I (p.Ser6Ile), rs587781112, ClinGen CA366745227, ClinVar RCV001063055, gnomAD rs587781112, AlphaMissense 0.08, MetaLR 0.47, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- S6N (p.Ser6Asn), rs587781112, ClinGen CA366745228, ClinVar RCV000564183, ClinVar RCV002527998, AlphaMissense 0.08, MetaLR 0.47, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- S6R (p.Ser6Arg), rs1221290124, ClinGen CA366745225, ClinVar RCV000567630, ClinVar RCV002528153, REVEL 0.48, CADD 3.23, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- S6T (p.Ser6Thr), rs587781112, ClinGen CA010279, ClinVar RCV000127469, ClinVar RCV003593914, REVEL 0.35, AlphaMissense 0.08, Benign
- S7* (p.Ser7Ter), rs587780048, ClinGen CA366745222, ClinVar RCV003452444, ClinVar RCV006473213, CADD 35.00, Pathogenic
- S7A (p.Ser7Ala), Ensembl rs1064793232, Likely benign
- S7L (p.Ser7Leu), rs587780048, ClinGen CA010809, NCI-TCGA Cosmic COSV5614, cosmic curated COSV56149, REVEL 0.30, CADD 10.90, Uncertain significance
- S7P (p.Ser7Pro), rs1064793232, ClinGen CA16618548, ClinVar RCV000482023, ClinVar RCV001851139, REVEL 0.39, CADD 4.38, Conflicting interpretations, not provided; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-pr
- S7T (p.Ser7Thr), Ensembl rs1064793232, Likely benign
- S7W (p.Ser7Trp), rs587780048, ClinGen CA046573, ClinVar RCV000219730, ClinVar RCV000806920, REVEL 0.33, CADD 11.90, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- S8C (p.Ser8Cys), ExAC rs772406975, TOPMed rs772406975, gnomAD rs772406975, REVEL 0.47, CADD 23.70, Uncertain significance
- S8G (p.Ser8Gly), rs772406975, ClinGen CA047469, ClinVar RCV002642451, ClinVar RCV004946028, REVEL 0.38, CADD 23.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- S8N (p.Ser8Asn), rs1352544158, ClinGen CA366745218, ClinVar RCV000699782, ClinVar RCV001187935, REVEL 0.34, AlphaMissense 0.08, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- S8R (p.Ser8Arg), rs1554306620, Ensembl rs1554306620, ClinGen CA366745204, ClinVar RCV003760945, AlphaMissense 0.27, MetaLR 0.62, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- S8T (p.Ser8Thr), rs1352544158, ClinGen CA366745219, ClinVar RCV000772979, TOPMed rs1352544158, AlphaMissense 0.08, MetaLR 0.54, Uncertain significance, Hereditary cancer-predisposing syndrome
- T9A (p.Thr9Ala), rs786202383, ClinGen CA011745, ClinVar RCV000165164, ClinVar RCV000411203, REVEL 0.28, CADD 14.90, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- T9I (p.Thr9Ile), rs1210073386, ClinGen CA366745199, ClinVar RCV000546264, ClinVar RCV000567566, AlphaMissense 0.12, MetaLR 0.66, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- T9K (p.Thr9Lys), rs1210073386, ClinGen CA366745201, ClinVar RCV003358292, AlphaMissense 0.12, MetaLR 0.66, Uncertain significance, Hereditary cancer-predisposing syndrome
- T9R (p.Thr9Arg), TOPMed rs1210073386, Uncertain significance
- T9S (p.Thr9Ser), TOPMed rs786202383, gnomAD rs786202383, Uncertain significance
- E10* (p.Glu10Ter), rs2128847171, ClinGen CA366745198, NCI-TCGA Cosmic COSV9976, cosmic curated COSV99764, AlphaMissense 0.11, MetaLR 0.71, Pathogenic
- E10A (p.Glu10Ala), rs878854050, ClinGen CA10582533, NCI-TCGA Cosmic COSV9976, cosmic curated COSV99763, REVEL 0.44, AlphaMissense 0.08, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- E10D (p.Glu10Asp), Ensembl rs876660608, Likely benign
- E10G (p.Glu10Gly), rs878854050, ClinGen CA366745195, ClinVar RCV004518738, AlphaMissense 0.08, MetaLR 0.68, Uncertain significance, Hereditary cancer-predisposing syndrome
- E10K (p.Glu10Lys), Ensembl rs2128847171, Pathogenic
- E10Q (p.Glu10Gln), Ensembl rs2128847171, Pathogenic
- E10V (p.Glu10Val), rs878854050, ClinGen CA366745194, ClinVar RCV001045627, ClinVar RCV001189337, AlphaMissense 0.08, MetaLR 0.68, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Lynch syndrome; not provided
- P11A (p.Pro11Ala), rs1554306608, ClinGen CA366745190, ClinVar RCV000574232, ClinVar RCV000706894, REVEL 0.26, AlphaMissense 0.08, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; not provided; Hereditary cancer-pr
- P11H (p.Pro11His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P11L (p.Pro11Leu), rs1291217267, ClinGen CA366745188, cosmic curated COSV10455, ClinVar RCV000781735, REVEL 0.33, CADD 8.92, Conflicting interpretations, not specified; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-p
- P11R (p.Pro11Arg), gnomAD rs1291217267, Uncertain significance
- P11S (p.Pro11Ser), rs1554306608, ClinGen CA366745189, ClinVar RCV001896371, ClinVar RCV006406999, AlphaMissense 0.08, MetaLR 0.43, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- A12D (p.Ala12Asp), rs1562702377, ClinGen CA366745181, ClinVar RCV003761004, ClinVar RCV004943150, AlphaMissense 0.14, MetaLR 0.79, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- A12G (p.Ala12Gly), Ensembl rs1562702377, Uncertain significance
- A12P (p.Ala12Pro), TOPMed rs1481967985, gnomAD rs1481967985, Uncertain significance
- A12S (p.Ala12Ser), TOPMed rs1481967985, gnomAD rs1481967985, Uncertain significance
- A12T (p.Ala12Thr), rs1481967985, ClinGen CA366745184, ClinVar RCV000629670, ClinVar RCV001179135, REVEL 0.48, CADD 25.30, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; not provided; Hereditary cancer-pr
- A12V (p.Ala12Val), rs1562702377, ClinGen CA366745180, ClinVar RCV000692044, ClinVar RCV005401574, AlphaMissense 0.14, MetaLR 0.79, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- K13* (p.Lys13Ter), Ensembl rs2128846939
- K13E (p.Lys13Glu), rs2128846939, ClinGen CA366745178, ClinVar RCV003759992, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- K13M (p.Lys13Met), Ensembl rs1785719173, Uncertain significance, Hereditary cancer-predisposing syndrome
- K13N (p.Lys13Asn), Ensembl rs2128846889, Likely benign
- K13T (p.Lys13Thr), rs1785719173, ClinGen CA366745176, ClinVar RCV001189254, Ensembl rs1785719173, AlphaMissense 0.12, MetaLR 0.72, Uncertain significance, Hereditary cancer-predisposing syndrome
- A14D (p.Ala14Asp), ExAC rs750524554, gnomAD rs750524554, REVEL 0.50, AlphaMissense 0.10, Uncertain significance
- A14G (p.Ala14Gly), rs750524554, ClinGen CA366745169, ClinVar RCV000630105, ClinVar RCV002331106, REVEL 0.43, AlphaMissense 0.10, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; not provided; Hereditary cancer-pr
- A14P (p.Ala14Pro), Ensembl rs876661039, Uncertain significance
- A14S (p.Ala14Ser), rs876661039, ClinGen CA10577359, ClinVar RCV000218140, ClinVar RCV000536772, REVEL 0.46, AlphaMissense 0.09, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; PMS2-related disorder; Hereditary
- A14T (p.Ala14Thr), rs876661039, ClinGen CA366745171, ClinVar RCV002323330, Ensembl rs876661039, AlphaMissense 0.09, MetaLR 0.63, Uncertain significance, Hereditary cancer-predisposing syndrome
- A14V (p.Ala14Val), rs750524554, ClinGen CA16618546, ClinVar RCV000483071, ClinVar RCV001035359, AlphaMissense 0.10, MetaLR 0.57, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Hereditary nonpolyposis c
- I15L (p.Ile15Leu), rs878854051, ClinGen CA366745168, ClinVar RCV003585761, AlphaMissense 0.20, MetaLR 0.91, Uncertain significance, Hereditary cancer-predisposing syndrome
- I15M (p.Ile15Met), rs876660499, ClinGen CA10578732, ClinVar RCV000214488, ClinVar RCV001854698, REVEL 0.85, CADD 24.30, Uncertain significance, not provided; Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-pr
- I15N (p.Ile15Asn), Ensembl rs2128846760
- I15T (p.Ile15Thr), Ensembl rs2128846760
- I15V (p.Ile15Val), rs878854051, ClinGen CA10582532, ClinVar RCV000228012, ClinVar RCV002327109, AlphaMissense 0.20, MetaLR 0.91, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- K16* (p.Lys16Ter), ExAC rs777845808, TOPMed rs777845808, gnomAD rs777845808, Uncertain significance
- K16E (p.Lys16Glu), rs777845808, ClinGen CA049915, ClinVar RCV000221254, ClinVar RCV000599996, REVEL 0.64, CADD 25.10, Uncertain significance, not provided; not specified; Hereditary nonpolyposis colorectal neoplasms
- K16I (p.Lys16Ile), rs1554306581, ClinGen CA366745159, ClinVar RCV002330734, ClinVar RCV003594212, AlphaMissense 0.24, MetaLR 0.76, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- K16N (p.Lys16Asn), Ensembl rs2128846698
- K16R (p.Lys16Arg), rs1554306581, ClinGen CA366745160, ClinVar RCV000629912, ClinVar RCV001023074, REVEL 0.20, AlphaMissense 0.24, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- K16T (p.Lys16Thr), rs1554306581, ClinGen CA366745161, ClinVar RCV003758403, AlphaMissense 0.24, MetaLR 0.76, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- P17A (p.Pro17Ala), rs552819358, ClinGen CA366745155, ClinVar RCV001321213, 1000Genomes rs552819358, AlphaMissense 0.20, MetaLR 0.71, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- P17H (p.Pro17His), rs1554306578, ClinGen CA366745154, ClinVar RCV000569635, Ensembl rs1554306578, AlphaMissense 0.25, MetaLR 0.76, Uncertain significance, Hereditary cancer-predisposing syndrome
- P17L (p.Pro17Leu), Ensembl rs1554306578, Uncertain significance
- P17R (p.Pro17Arg), rs1554306578, ClinGen CA366745153, ClinVar RCV002335983, ClinVar RCV003594217, AlphaMissense 0.25, MetaLR 0.76, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- P17S (p.Pro17Ser), 1000Genomes rs552819358, ExAC rs552819358, gnomAD rs552819358, REVEL 0.53, AlphaMissense 0.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- I18F (p.Ile18Phe), rs63750123, ClinGen CA366745150, ClinVar RCV001896168, 1000Genomes rs63750123, AlphaMissense 0.29, MetaLR 0.77, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- I18L (p.Ile18Leu), 1000Genomes rs63750123, ESP rs63750123, ExAC rs63750123, TOPMed rs63750123, Benign, in LYNCH4
- I18T (p.Ile18Thr), rs201343342, ClinGen CA012293, ClinVar RCV000034630, ClinVar RCV000115698, REVEL 0.94, CADD 26.40, Benign, in LYNCH4
- I18V (p.Ile18Val), rs63750123, ClinGen CA012251, cosmic curated COSV56149, ClinVar RCV000034629, REVEL 0.64, AlphaMissense 0.29, Benign, in LYNCH4
- D19G (p.Asp19Gly), rs1554306564, ClinGen CA366745142, ClinVar RCV000566698, ClinVar RCV001211840, AlphaMissense 0.72, MetaLR 0.82, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- D19H (p.Asp19His), rs1554306568, ClinGen CA366745145, ClinVar RCV000575185, ClinVar RCV000700522, REVEL 0.71, AlphaMissense 0.66, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- D19N (p.Asp19Asn), rs1554306568, ClinGen CA366745146, ClinVar RCV002344892, Ensembl rs1554306568, AlphaMissense 0.66, MetaLR 0.83, Uncertain significance, Hereditary cancer-predisposing syndrome
- D19V (p.Asp19Val), Ensembl rs1554306564, REVEL 0.85, AlphaMissense 0.72, Uncertain significance, Hereditary cancer-predisposing syndrome
- D19Y (p.Asp19Tyr), rs1554306568, ClinGen CA366745144, ClinVar RCV002009549, ClinVar RCV002346284, AlphaMissense 0.66, MetaLR 0.83, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- R20G (p.Arg20Gly), rs573374779, ClinGen CA050459, ClinVar RCV000468998, ClinVar RCV000561984, REVEL 0.32, CADD 22.40, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Lynch syndrome; not provided
- R20L (p.Arg20Leu), 1000Genomes rs10254120, ESP rs10254120, ExAC rs10254120, TOPMed rs10254120, Benign, in LYNCH4
- R20P (p.Arg20Pro), rs10254120, ClinGen CA10578731, ClinVar RCV000219300, ClinVar RCV002229322, AlphaMissense 0.18, MetaLR 0.65, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- R20Q (p.Arg20Gln), rs10254120, ClinGen CA012376, cosmic curated COSV56151, ClinVar RCV000034632, REVEL 0.43, AlphaMissense 0.18, Benign, Lynch syndrome 4
- R20W (p.Arg20Trp), rs573374779, ClinGen CA050487, cosmic curated COSV56151, ClinVar RCV000198784, REVEL 0.58, CADD 26.10, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- K21M (p.Lys21Met), TOPMed rs1458424619, Uncertain significance
- K21N (p.Lys21Asn), rs772643900, ClinGen CA366745132, ClinVar RCV001025229, ClinVar RCV001873393, REVEL 0.32, CADD 23.50, Uncertain significance, Hereditary cancer-predisposing syndrome
- K21R (p.Lys21Arg), rs1458424619, ClinGen CA366745134, ClinVar RCV001181206, TOPMed rs1458424619, AlphaMissense 0.14, MetaLR 0.67, Uncertain significance, Hereditary cancer-predisposing syndrome
- K21T (p.Lys21Thr), TOPMed rs1458424619, Uncertain significance
- S22* (p.Ser22Ter), rs767028531, ClinGen CA366745128, ClinVar RCV001233504, ClinVar RCV002375243, CADD 41.00, Pathogenic
- S22A (p.Ser22Ala), gnomAD rs1403470297
- S22L (p.Ser22Leu), rs767028531, ClinGen CA366745127, ClinVar RCV001896313, ExAC rs767028531, REVEL 0.78, CADD 28.40, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- S22T (p.Ser22Thr), gnomAD rs1403470297, REVEL 0.58, CADD 24.60
- V23A (p.Val23Ala), Ensembl rs1060503114, Uncertain significance
- V23D (p.Val23Asp), Ensembl rs1060503114, Uncertain significance
- V23F (p.Val23Phe), rs374830220, ClinGen CA366745125, ClinVar RCV002369488, ClinVar RCV004808288, AlphaMissense 0.72, MetaLR 0.83, Uncertain significance, Lynch syndrome; Hereditary cancer-predisposing syndrome
- V23G (p.Val23Gly), rs1060503114, ClinGen CA16612157, cosmic curated COSV10584, ClinVar RCV002230426, AlphaMissense 0.81, MetaLR 0.78, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- V23I (p.Val23Ile), rs374830220, ClinGen CA366745126, ClinVar RCV003028318, AlphaMissense 0.72, MetaLR 0.83, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- V23L (p.Val23Leu), rs374830220, ClinGen CA050868, ClinVar RCV001177036, ClinVar RCV002559714, REVEL 0.73, AlphaMissense 0.72, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- H24D (p.His24Asp), Ensembl rs2128846151, Uncertain significance
- H24L (p.His24Leu), rs139233015, ClinGen CA366745119, ClinVar RCV001904712, 1000Genomes rs139233015, AlphaMissense 0.79, MetaLR 0.79, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- H24N (p.His24Asn), Ensembl rs2128846151, Uncertain significance
- H24P (p.His24Pro), rs139233015, ClinGen CA012663, ClinVar RCV000166828, ClinVar RCV000459353, REVEL 0.92, AlphaMissense 0.79, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- H24Q (p.His24Gln), Ensembl rs2128846096
- H24R (p.His24Arg), rs139233015, ClinGen CA051360, ClinVar RCV001524797, ClinVar RCV002568080, REVEL 0.88, AlphaMissense 0.79, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- H24Y (p.His24Tyr), NCI-TCGA Cosmic COSV5615, cosmic curated COSV56151, Ensembl rs2128846151, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q25* (p.Gln25Ter), rs1554306528, ClinGen CA366745114, NCI-TCGA Cosmic COSV5615, cosmic curated COSV56151, AlphaMissense 0.16, MetaLR 0.77, Pathogenic
- Q25E (p.Gln25Glu), rs1554306528, ClinGen CA366745115, NCI-TCGA Cosmic COSV5615, ClinVar RCV002380513, AlphaMissense 0.16, MetaLR 0.77, Uncertain significance, Hereditary cancer-predisposing syndrome
- Q25H (p.Gln25His), rs1554306525, ClinGen CA366745109, ClinVar RCV000584040, ClinVar RCV000765970, AlphaMissense 0.36, MetaLR 0.70, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- Q25L (p.Gln25Leu), Ensembl rs2128846036
- Q25R (p.Gln25Arg), Ensembl rs2128846036, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- I26F (p.Ile26Phe), rs1412094620, ClinGen CA366745106, ClinVar RCV001316641, TOPMed rs1412094620, AlphaMissense 0.69, MetaLR 0.87, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- I26L (p.Ile26Leu), rs1412094620, ClinGen CA366745108, ClinVar RCV001038065, TOPMed rs1412094620, AlphaMissense 0.69, MetaLR 0.87, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- I26N (p.Ile26Asn), Ensembl rs1583419301, Uncertain significance
- I26T (p.Ile26Thr), rs1583419301, ClinGen CA366745104, ClinVar RCV001026827, ClinVar RCV001232308, AlphaMissense 1.00, MetaLR 0.89, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- I26V (p.Ile26Val), TOPMed rs1412094620, gnomAD rs1412094620, REVEL 0.81, AlphaMissense 0.69, Uncertain significance
- C27* (p.Cys27Ter), rs2128845860, ClinGen CA366745095, ClinVar RCV002427905, AlphaMissense 0.98, MetaLR 0.74, Pathogenic
- C27F (p.Cys27Phe), rs2128845886, ClinGen CA366745096, ClinVar RCV001995725, Ensembl rs2128845886, AlphaMissense 0.95, MetaLR 0.81, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms
- C27G (p.Cys27Gly), Ensembl rs2128845910
- C27S (p.Cys27Ser), Ensembl rs2128845886, Uncertain significance
- C27W (p.Cys27Trp), rs2128845860, ClinGen CA366745094, ClinVar RCV004518753, Ensembl rs2128845860, AlphaMissense 0.98, MetaLR 0.74, Uncertain significance, Hereditary cancer-predisposing syndrome
- C27Y (p.Cys27Tyr), rs2128845886, ClinGen CA366745097, ClinVar RCV001369699, ClinVar RCV005403062, REVEL 0.83, AlphaMissense 0.95, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- S28A (p.Ser28Ala), rs587781908, ClinGen CA366745092, ClinVar RCV001914289, ClinVar RCV002425254, AlphaMissense 0.94, MetaLR 0.85, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- S28C (p.Ser28Cys), cosmic curated COSV10584, Ensembl rs1785707505, Uncertain significance
- S28F (p.Ser28Phe), rs1785707505, ClinGen CA366745089, ClinVar RCV001337225, ClinVar RCV002438766, AlphaMissense 0.93, MetaLR 0.88, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- S28P (p.Ser28Pro), rs587781908, ClinGen CA012958, ClinVar RCV000130248, ClinVar RCV000233273, REVEL 0.93, AlphaMissense 0.94, Likely benign
- S28T (p.Ser28Thr), ExAC rs587781908, TOPMed rs587781908, gnomAD rs587781908, Uncertain significance
- G29A (p.Gly29Ala), rs146176004, ClinGen CA013092, ClinVar RCV000034637, ClinVar RCV000115707, REVEL 0.82, CADD 25.10, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- G29E (p.Gly29Glu), 1000Genomes rs146176004, ESP rs146176004, ExAC rs146176004, TOPMed rs146176004, Uncertain significance, Hereditary cancer-predisposing syndrome
- G29R (p.Gly29Arg), rs1583419271, ClinGen CA366745088, ClinVar RCV001018079, ClinVar RCV001046681, AlphaMissense 0.97, MetaLR 0.60, Uncertain significance, not specified
- G29V (p.Gly29Val), 1000Genomes rs146176004, ESP rs146176004, ExAC rs146176004, TOPMed rs146176004, Benign
- Q30* (p.Gln30Ter), rs141577476, ClinGen CA013182, ClinVar RCV000131992, ClinVar RCV000475400, AlphaMissense 0.81, MetaLR 0.61, Pathogenic
- Q30E (p.Gln30Glu), rs141577476, ClinGen CA366745083, cosmic curated COSV10584, ClinVar RCV001185928, REVEL 0.50, AlphaMissense 0.81, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- Q30H (p.Gln30His), TOPMed rs1413534855, Likely benign
- Q30K (p.Gln30Lys), rs141577476, ClinGen CA052131, ClinVar RCV000227509, ClinVar RCV001018478, REVEL 0.83, AlphaMissense 0.81, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- Q30L (p.Gln30Leu), TOPMed rs56203955, gnomAD rs56203955, Uncertain significance
- Q30P (p.Gln30Pro), rs56203955, ClinGen CA153249729, cosmic curated COSV56151, ClinVar RCV004509666, AlphaMissense 0.83, MetaLR 0.53, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- Q30R (p.Gln30Arg), rs56203955, ClinGen CA013191, ClinVar RCV000164904, ClinVar RCV000198290, REVEL 0.81, AlphaMissense 0.83, Conflicting interpretations, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V31A (p.Val31Ala), rs2128845590, ClinGen CA366745076, cosmic curated COSV10941, ClinVar RCV002371541, AlphaMissense 0.84, MetaLR 0.60, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- V31E (p.Val31Glu), Ensembl rs2128845590, Uncertain significance
- V31G (p.Val31Gly), rs2128845590, ClinGen CA366745075, ClinVar RCV002371544, Ensembl rs2128845590, AlphaMissense 0.84, MetaLR 0.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- V31L (p.Val31Leu), rs786203763, Ensembl rs786203763, ClinGen CA013264, ClinVar RCV000167210, REVEL 0.79, CADD 24.70, Uncertain significance, PMS2-related disorder; Hereditary nonpolyposis colorectal neoplasms; Hereditary
- V31M (p.Val31Met), rs786203763, ClinGen CA366745078, ClinVar RCV000803040, ClinVar RCV002442672, REVEL 0.72, CADD 25.20, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V32A (p.Val32Ala), rs2536587189, ClinGen CA366745071, ClinVar RCV002385297, ClinVar RCV003594250, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- V32I (p.Val32Ile), rs977251189, ClinGen CA366745074, cosmic curated COSV10722, ClinVar RCV000564962, REVEL 0.16, CADD 18.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- V32L (p.Val32Leu), rs977251189, TOPMed rs977251189, gnomAD rs977251189, ClinGen CA16612292, REVEL 0.67, CADD 22.70, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
- L33P (p.Leu33Pro), cosmic curated COSV56150, Ensembl rs1554306467, Uncertain significance
- L33Q (p.Leu33Gln), Ensembl rs1554306467, Uncertain significance
- L33R (p.Leu33Arg), rs1554306467, ClinGen CA366745067, ClinVar RCV000563426, ClinVar RCV005091436, AlphaMissense 0.74, MetaLR 0.64, Uncertain significance, Hereditary nonpolyposis colorectal neoplasms; Hereditary cancer-predisposing syn
- L33V (p.Leu33Val), rs878854061, ClinGen CA366745068, ClinVar RCV001184883, gnomAD rs878854061, REVEL 0.39, CADD 23.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- S34C (p.Ser34Cys), Ensembl rs730881912, Uncertain significance
- S34G (p.Ser34Gly), rs730881912, ClinGen CA366745064, ClinVar RCV002440875, ClinVar RCV004808122, REVEL 0.43, CADD 22.30, Uncertain significance, Lynch syndrome; Hereditary cancer-predisposing syndrome
- S34I (p.Ser34Ile), rs370612538, ClinGen CA009103, ClinVar RCV000166613, ClinVar RCV000231923, REVEL 0.73, AlphaMissense 0.65, Conflicting interpretations, not provided; Lynch syndrome; Hereditary nonpolyposis colorectal neoplasms
- S34N (p.Ser34Asn), rs370612538, ClinGen CA366745062, ClinVar RCV001373699, ClinVar RCV002368209, REVEL 0.29, AlphaMissense 0.65, Uncertain significance, Hereditary cancer-predisposing syndrome; Hereditary nonpolyposis colorectal neop
Public PMS2 analysis runs
- PMS2 analysis run — PMS2 (4,022 variants) — completed 2026-08-10