NBN (Nibrin) variants and mutations
NBN (also known as Nibrin) is a human protein-coding gene encoding a nibrin protein. It recruits and organizes the MRE11-RAD50 complex at DNA double-strand breaks and helps activate ATM-dependent DNA-damage responses. Biallelic loss-of-function variants cause Nijmegen breakage syndrome with microcephaly, immunodeficiency, chromosome instability, and high cancer risk. This analysis covers 2,307 NBN variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes neurodegenerative disease, migraine disorder, and gastric cancer. Example NBN variants include M1I, M1T, and W2*.
Variant analysis overview
- Gene: NBN
- Protein: Nibrin
- UniProt accession: O60934
- Organism: Homo sapiens
- Variants analyzed: 2307
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,145 unspecified-consequence records; 63 missense variants; 66 synonymous variants; 14 frameshift variants; 1 protein altering variant; 5 splice-region variants; 2 in-frame deletions; 5 stop-gained variants; 6 substitution
- Prediction scores: 1,794 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, migraine disorder, gastric cancer, lung cancer, intelligence, hepatocellular carcinoma, lung carcinoma, breast carcinoma, colorectal carcinoma, acute myeloid leukemia, pancreatic neoplasm, familial pancreatic carcinoma.
Protein structure and variant hotspots
- Protein features: 3 domains; 12 post-translational modification sites.
- Structural context: 629 variants have structural context.
- PTM context: 36 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 NBN variants
Examples include M1I, M1T, W2*, W2C, W2S, W2X, K3*, K3N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1554569682, ClinGen CA371664229, ClinVar RCV000525671, MetaLR 0.44, MetaSVM -0.05, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Aplastic anemia
- M1T (p.Met1Thr), rs746422391, ClinGen CA4803109, ClinVar RCV000484157, ClinVar RCV000695139, MetaLR 0.52, MetaSVM 0.09, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- W2* (p.Trp2Ter), rs1812244679, ClinGen CA371664218, ClinVar RCV001270990, ClinVar RCV002537743, CADD 37.00, Pathogenic
- W2C (p.Trp2Cys), rs876661130, ClinGen CA371664215, ClinVar RCV002378236, REVEL 0.47, CADD 26.90, Uncertain significance, Hereditary cancer-predisposing syndrome
- W2S (p.Trp2Ser), rs1812244679, ClinGen CA371664219, ClinVar RCV002357998, REVEL 0.46, CADD 26.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- W2X, rs876661130, Likely pathogenic
- K3* (p.Lys3Ter), rs779098734, ClinGen CA4803108, ClinVar RCV000581960, ClinVar RCV000707330, CADD 39.00, Pathogenic
- K3N (p.Lys3Asn), rs1586116169, ClinGen CA371664203, ClinVar RCV002297662, Ensembl rs1586116169, AlphaMissense 0.61, MetaLR 0.09, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- K3R (p.Lys3Arg), ExAC rs771376603, REVEL 0.06, CADD 18.80
- K3T (p.Lys3Thr), rs771376603, ClinGen CA371664207, ClinVar RCV002376337, REVEL 0.07, CADD 19.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- L4M (p.Leu4Met), rs1426394881, ClinGen CA371664199, ClinVar RCV003617330, AlphaMissense 0.36, MetaLR 0.24, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- L4P (p.Leu4Pro), rs748090667, ClinGen CA16612508, ClinVar RCV000463112, ClinVar RCV000569693, AlphaMissense 0.98, MetaLR 0.28, Uncertain significance, Aplastic anemia; not provided; Hereditary cancer-predisposing syndrome
- L4R (p.Leu4Arg), rs748090667, ClinGen CA181286161, ClinVar RCV000546827, ClinVar RCV000565981, REVEL 0.44, AlphaMissense 0.98, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- L4V (p.Leu4Val), rs1426394881, ClinGen CA371664198, ClinVar RCV001214168, ClinVar RCV003163634, REVEL 0.31, AlphaMissense 0.36, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- L5P (p.Leu5Pro), rs1586116142, ClinGen CA371664189, ClinVar RCV002033629, Ensembl rs1586116142, AlphaMissense 0.76, MetaLR 0.10, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- L5Q (p.Leu5Gln), rs1586116142, ClinGen CA371664190, ClinVar RCV000793304, Ensembl rs1586116142, AlphaMissense 0.76, MetaLR 0.10, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- L5R (p.Leu5Arg), rs1586116142, ClinGen CA371664187, ClinVar RCV002389908, AlphaMissense 0.76, MetaLR 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome
- L5V (p.Leu5Val), rs1563588747, ClinGen CA371664193, ClinVar RCV000776598, ClinVar RCV001337830, AlphaMissense 0.05, MetaLR 0.05, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- P6A (p.Pro6Ala), rs730881859, ClinGen CA4803106, ClinVar RCV001208049, ClinVar RCV002402609, REVEL 0.16, AlphaMissense 0.20, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; not specified; Hereditar
- P6L (p.Pro6Leu), rs876658432, ClinGen CA10578821, ClinVar RCV000222282, ClinVar RCV001233526, AlphaMissense 0.52, MetaLR 0.18, Uncertain significance, Acute lymphoid leukemia; Microcephaly, normal intelligence and immunodeficiency
- P6S (p.Pro6Ser), rs730881859, ClinGen CA299642, NCI-TCGA Cosmic COSV5537, ClinVar RCV000160798, REVEL 0.10, AlphaMissense 0.20, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; not provided
- P6T (p.Pro6Thr), rs730881859, ClinGen CA371664186, ClinVar RCV001052228, ExAC rs730881859, AlphaMissense 0.20, MetaLR 0.07, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- A7P (p.Ala7Pro), rs587780779, ClinGen CA371664176, ClinVar RCV001875577, gnomAD rs587780779, AlphaMissense 0.17, MetaLR 0.08, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- A7S (p.Ala7Ser), gnomAD rs587780779, Uncertain significance
- A7T (p.Ala7Thr), rs587780779, ClinGen CA332820, ClinVar RCV000123211, ClinVar RCV001014001, REVEL 0.07, AlphaMissense 0.17, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- A7V (p.Ala7Val), rs781057669, ClinGen CA181286152, ClinVar RCV001236445, ClinVar RCV002418811, REVEL 0.03, CADD 4.26, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- A8G (p.Ala8Gly), rs1060503459, ClinGen CA371664163, ClinVar RCV001578686, Ensembl rs1060503459, REVEL 0.11, AlphaMissense 0.24, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- A8P (p.Ala8Pro), rs2129938188, ClinGen CA371664167, ClinVar RCV003508147, AlphaMissense 0.14, MetaLR 0.07, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- A8T (p.Ala8Thr), rs2129938188, ClinGen CA371664168, NCI-TCGA Cosmic COSV5537, ClinVar RCV003165078, REVEL 0.09, AlphaMissense 0.14, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- A8V (p.Ala8Val), rs1060503459, ClinGen CA16612557, ClinVar RCV000457469, ClinVar RCV001805079, AlphaMissense 0.24, MetaLR 0.16, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- G9D (p.Gly9Asp), rs1554569664, ClinGen CA371664158, ClinVar RCV003869323, ClinVar RCV004787071, AlphaMissense 0.16, MetaLR 0.11, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; not provided; Hereditary
- G9S (p.Gly9Ser), rs2129938127, ClinGen CA371664161, ClinVar RCV001899681, ClinVar RCV003164209, AlphaMissense 0.17, MetaLR 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Aplastic anemia; Microcephaly, normal i
- G9V (p.Gly9Val), rs1554569664, ClinGen CA371664155, ClinVar RCV000535302, Ensembl rs1554569664, AlphaMissense 0.16, MetaLR 0.11, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- P10A (p.Pro10Ala), rs758228844, ClinGen CA371664152, ClinVar RCV001971163, ExAC rs758228844, REVEL 0.02, CADD 2.50, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- P10S (p.Pro10Ser), rs758228844, ClinGen CA371664153, ClinVar RCV002568100, ClinVar RCV004651684, REVEL 0.01, CADD 4.08, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- P10T (p.Pro10Thr), rs758228844, ClinGen CA4803102, ClinVar RCV000795693, ExAC rs758228844, REVEL 0.02, CADD 4.16, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- A11T (p.Ala11Thr), rs764914981, ClinGen CA4803100, ClinVar RCV003015552, ClinVar RCV004946123, REVEL 0.08, CADD 21.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- A11V (p.Ala11Val), rs1812242013, ClinGen CA371664134, ClinVar RCV002255964, ClinVar RCV005419420, REVEL 0.15, CADD 24.20, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified
- G12A (p.Gly12Ala), rs730881860, ClinGen CA299645, ClinVar RCV000160799, ClinVar RCV001208076, AlphaMissense 0.11, MetaLR 0.07, Uncertain significance, not provided; Microcephaly, normal intelligence and immunodeficiency
- G12E (p.Gly12Glu), rs730881860, ClinGen CA195890, ClinVar RCV000166444, ClinVar RCV001220952, REVEL 0.01, AlphaMissense 0.11, Uncertain significance, Hereditary cancer-predisposing syndrome
- G12R (p.Gly12Arg), rs878854511, ClinGen CA371664132, ClinVar RCV000775704, TOPMed rs878854511, REVEL 0.03, CADD 16.50, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- G13* (p.Gly13Ter), NCI-TCGA Cosmic COSV9962, Variant assessed as somatic; high impact.
- G13R (p.Gly13Arg), rs757112911, ClinGen CA4803099, ClinVar RCV000526745, ClinVar RCV001184070, REVEL 0.15, CADD 33.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- E14* (p.Glu14Ter), rs745439506, ClinGen CA371663736, ClinVar RCV003470296, AlphaMissense 0.19, MetaLR 0.06, Likely pathogenic
- E14D (p.Glu14Asp), rs957561936, ClinGen CA371663729, ClinVar RCV001369869, ClinVar RCV002329387, REVEL 0.03, CADD 11.10, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- E14K (p.Glu14Lys), rs745439506, ClinGen CA4803065, ClinVar RCV000216199, ClinVar RCV001540678, REVEL 0.07, AlphaMissense 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- E14Q (p.Glu14Gln), rs745439506, ClinGen CA371663738, ClinVar RCV003618415, AlphaMissense 0.19, MetaLR 0.06, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- P15L (p.Pro15Leu), rs1586112154, ClinGen CA371663709, ClinVar RCV001022588, ClinVar RCV003507350, AlphaMissense 0.20, MetaLR 0.09, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- P15S (p.Pro15Ser), rs1563584802, ClinGen CA371663717, ClinVar RCV002039218, Ensembl rs1563584802, AlphaMissense 0.12, MetaLR 0.04, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- P15T (p.Pro15Thr), Ensembl rs1563584802, Uncertain significance
- Y16* (p.Tyr16Ter), rs2129926091, ClinGen CA371663676, ClinVar RCV001385181, ClinVar RCV003399206, Pathogenic
- Y16C (p.Tyr16Cys), rs864622726, ClinGen CA371663697, ClinVar RCV001023075, ClinVar RCV001800935, REVEL 0.06, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- Y16S (p.Tyr16Ser), rs864622726, ClinGen CA348276, ClinVar RCV000204001, Ensembl rs864622726, AlphaMissense 0.07, MetaLR 0.07, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- R17I (p.Arg17Ile), NCI-TCGA Cosmic COSV5537, REVEL 0.19, CADD 26.90, Variant assessed as somatic; moderate impact.
- L18I (p.Leu18Ile), rs587781939, ClinGen CA166136, ClinVar RCV000130303, ClinVar RCV000232902, REVEL 0.16, CADD 25.60, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; not provided
- L19* (p.Leu19Ter), rs749263651, ClinGen CA371663635, ClinVar RCV001814388, ExAC rs749263651, AlphaMissense 0.41, MetaLR 0.25, Likely pathogenic
- L19V (p.Leu19Val), rs1586112097, ClinGen CA371663638, ClinVar RCV001295567, ClinVar RCV002350515, AlphaMissense 0.14, MetaLR 0.16, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- L19W (p.Leu19Trp), rs749263651, ClinGen CA4803063, ClinVar RCV000562197, ClinVar RCV001853722, REVEL 0.53, AlphaMissense 0.41, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- T20I (p.Thr20Ile), rs1563584711, ClinGen CA371663612, ClinVar RCV000685243, Ensembl rs1563584711, AlphaMissense 0.19, MetaLR 0.07, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- T20S (p.Thr20Ser), rs1563584711, ClinGen CA371663613, ClinVar RCV002357946, REVEL 0.08, AlphaMissense 0.19, Uncertain significance, Hereditary cancer-predisposing syndrome
- G21S (p.Gly21Ser), rs1586112049, ClinGen CA371663608, ClinVar RCV001025001, Ensembl rs1586112049, AlphaMissense 0.13, MetaLR 0.23, Uncertain significance, Hereditary cancer-predisposing syndrome
- G21V (p.Gly21Val), Ensembl rs2129925919, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- V22F (p.Val22Phe), rs369910645, ClinGen CA371663582, ClinVar RCV000540870, ClinVar RCV004943965, AlphaMissense 0.07, MetaLR 0.08, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- V22I (p.Val22Ile), rs369910645, ClinGen CA4803061, ClinVar RCV000227804, ClinVar RCV000572001, REVEL 0.03, AlphaMissense 0.07, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- Y24C (p.Tyr24Cys), rs1812137176, ClinGen CA371663508, ClinVar RCV003020673, AlphaMissense 0.87, MetaLR 0.85, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- Y24D (p.Tyr24Asp), rs1812137322, ClinGen CA371663511, ClinVar RCV001190382, Ensembl rs1812137322, AlphaMissense 0.93, MetaLR 0.87, Uncertain significance, Hereditary cancer-predisposing syndrome
- Y24S (p.Tyr24Ser), rs1812137176, ClinGen CA371663491, ClinVar RCV001350461, ClinVar RCV005438979, AlphaMissense 0.87, MetaLR 0.85, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- V25F (p.Val25Phe), rs587781748, ClinGen CA371663475, ClinVar RCV000693538, ClinVar RCV001026395, REVEL 0.53, CADD 12.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- V25I (p.Val25Ile), rs587781748, ClinGen CA294139, ClinVar RCV000129954, ClinVar RCV000212726, REVEL 0.29, CADD 0.07, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not specified; not provided
- V26A (p.Val26Ala), rs781536675, ClinGen CA4803059, ClinVar RCV000820194, ClinVar RCV002408973, REVEL 0.57, CADD 27.40, Uncertain significance, Aplastic anemia; Microcephaly, normal intelligence and immunodeficiency; Heredit
- V26F (p.Val26Phe), rs752964949, ClinGen CA371663454, ClinVar RCV000807597, ClinVar RCV002397652, REVEL 0.46, CADD 25.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- V26I (p.Val26Ile), rs752964949, ClinGen CA181281141, ClinVar RCV001921957, ExAC rs752964949, REVEL 0.28, CADD 25.00, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- V26L (p.Val26Leu), ExAC rs752964949, gnomAD rs752964949, REVEL 0.35, CADD 25.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- G27A (p.Gly27Ala), rs755171159, ClinGen CA371663425, ClinVar RCV003618612, AlphaMissense 1.00, MetaLR 1.00, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- G27E (p.Gly27Glu), rs755171159, ClinGen CA371663426, ClinVar RCV001039445, ClinVar RCV003478669, REVEL 0.93, AlphaMissense 1.00, Uncertain significance, not provided; Aplastic anemia; Microcephaly, normal intelligence and immunodefic
- G27V (p.Gly27Val), rs755171159, ClinGen CA4803058, ClinVar RCV000228051, ClinVar RCV000568019, REVEL 0.91, AlphaMissense 1.00, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- R28G (p.Arg28Gly), rs1563584545, ClinGen CA371663424, ClinVar RCV001315586, ClinVar RCV004649312, AlphaMissense 0.98, MetaLR 0.72, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- R28K (p.Arg28Lys), rs876658581, ClinGen CA10578816, ClinVar RCV000218413, ClinVar RCV000694610, REVEL 0.76, CADD 25.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Aplastic anemia; Microcephaly, normal i
- R28S (p.Arg28Ser), Ensembl rs1812135749
- K29R (p.Lys29Arg), rs1554569112, ClinGen CA371663405, ClinVar RCV000556426, ClinVar RCV001178803, AlphaMissense 0.13, MetaLR 0.67, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- N30H (p.Asn30His), Ensembl rs2129925520, REVEL 0.34, CADD 25.40
- N30S (p.Asn30Ser), rs587781450, ClinGen CA164297, ClinVar RCV000129374, Ensembl rs587781450, REVEL 0.26, CADD 24.60, Uncertain significance, Hereditary cancer-predisposing syndrome
- C31F (p.Cys31Phe), rs1377520302, ClinGen CA371663330, ClinVar RCV003617310, AlphaMissense 0.32, MetaLR 0.16, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- C31R (p.Cys31Arg), rs876658553, ClinGen CA10578815, ClinVar RCV000218564, ClinVar RCV001363922, REVEL 0.54, CADD 27.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- C31S (p.Cys31Ser), rs1377520302, ClinGen CA371663332, ClinVar RCV000798750, ClinVar RCV004027966, REVEL 0.31, AlphaMissense 0.32, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- C31Y (p.Cys31Tyr), rs1377520302, ClinGen CA371663334, ClinVar RCV000692664, TOPMed rs1377520302, AlphaMissense 0.32, MetaLR 0.16, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- A32V (p.Ala32Val), Ensembl rs2129925368
- I33L (p.Ile33Leu), rs1563584435, ClinGen CA371663302, ClinVar RCV003040624, AlphaMissense 0.12, MetaLR 0.72, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- I33M (p.Ile33Met), rs1172365532, ClinGen CA371663283, ClinVar RCV001035513, ClinVar RCV003160205, REVEL 0.65, CADD 24.10, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- I33N (p.Ile33Asn), rs2488369193, ClinGen CA371663293, ClinVar RCV002387463, Uncertain significance, Hereditary cancer-predisposing syndrome
- I33V (p.Ile33Val), rs1563584435, ClinGen CA371663305, ClinVar RCV000709064, ClinVar RCV001188198, AlphaMissense 0.12, MetaLR 0.72, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- L34M (p.Leu34Met), rs1586111855, ClinGen CA371663278, ClinVar RCV001016978, Ensembl rs1586111855, AlphaMissense 0.20, MetaLR 0.66, Uncertain significance, Hereditary cancer-predisposing syndrome
- L34R (p.Leu34Arg), rs1012390181, ClinGen CA181281117, ClinVar RCV000549829, ClinVar RCV002298649, AlphaMissense 0.33, MetaLR 0.67, Uncertain significance, Hereditary cancer-predisposing syndrome; not specified; Microcephaly, normal int
- I35F (p.Ile35Phe), rs2129925202, ClinGen CA371663262, ClinVar RCV001902915, ClinVar RCV005684798, AlphaMissense 0.44, MetaLR 0.70, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- I35M (p.Ile35Met), rs78870221, ClinGen CA4803056, ClinVar RCV000216738, ClinVar RCV000533679, REVEL 0.63, CADD 22.60, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- I35T (p.Ile35Thr), rs1554569095, ClinGen CA658683519, ClinVar RCV000579707, Ensembl rs1554569095, REVEL 0.79, CADD 26.20, Likely benign, Hereditary cancer-predisposing syndrome
- E36* (p.Glu36Ter), Ensembl rs2129925113
- E36A (p.Glu36Ala), NCI-TCGA Cosmic COSV5537, Variant assessed as somatic; moderate impact.
- N37D (p.Asn37Asp), rs876658411, ClinGen CA10578814, ClinVar RCV000217641, ClinVar RCV000469351, REVEL 0.06, CADD 6.83, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- N37K (p.Asn37Lys), rs2488368993, ClinGen CA371663197, ClinVar RCV002726667, ClinVar RCV005382464, REVEL 0.04, CADD 0.14, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- D38H (p.Asp38His), rs876659565, ClinGen CA10578813, ClinVar RCV000219457, ClinVar RCV001372465, REVEL 0.60, CADD 26.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- D38V (p.Asp38Val), rs2129925061, ClinGen CA371663158, ClinVar RCV002025236, ClinVar RCV003130657, REVEL 0.77, CADD 27.40, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- D38Y (p.Asp38Tyr), rs876659565, ClinGen CA371663183, ClinVar RCV002579210, ClinVar RCV005045301, REVEL 0.68, CADD 26.80, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Acute lymphoid leukemia
- Q39* (p.Gln39Ter), rs377730553, ClinGen CA371663153, ClinVar RCV001186594, ClinVar RCV001862938, CADD 36.00, Pathogenic
- Q39E (p.Gln39Glu), rs377730553, ClinGen CA164970, ClinVar RCV000129719, ClinVar RCV000820955, REVEL 0.55, CADD 23.80, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- Q39K (p.Gln39Lys), rs377730553, ClinGen CA181281098, ClinVar RCV000636775, ClinVar RCV001010019, REVEL 0.54, CADD 24.30, Uncertain significance, Hereditary cancer-predisposing syndrome; Aplastic anemia; Microcephaly, normal i
- Q39L (p.Gln39Leu), rs765551184, ClinGen CA371663142, ClinVar RCV001059176, ClinVar RCV002327330, AlphaMissense 0.28, MetaLR 0.59, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- Q39R (p.Gln39Arg), rs765551184, ClinGen CA4803054, ClinVar RCV002632077, ClinVar RCV003167543, REVEL 0.51, AlphaMissense 0.28, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- S40L (p.Ser40Leu), rs587781530, ClinGen CA164600, ClinVar RCV000129524, ClinVar RCV000232275, REVEL 0.88, CADD 28.30, Uncertain significance, Acute lymphoid leukemia; Microcephaly, normal intelligence and immunodeficiency
- I41F (p.Ile41Phe), rs1563584220, ClinGen CA371663107, ClinVar RCV001856077, Ensembl rs1563584220, REVEL 0.45, CADD 24.60, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- I41M (p.Ile41Met), rs887413615, ClinGen CA371663095, ClinVar RCV001976614, Ensembl rs887413615, AlphaMissense 0.88, MetaLR 0.20, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- I41S (p.Ile41Ser), rs1554569074, ClinGen CA371663098, ClinVar RCV000575311, Ensembl rs1554569074, AlphaMissense 0.99, MetaLR 0.35, Uncertain significance, Hereditary cancer-predisposing syndrome
- I41T (p.Ile41Thr), rs1554569074, ClinGen CA371663101, ClinVar RCV001231264, Ensembl rs1554569074, AlphaMissense 0.99, MetaLR 0.35, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- I41V (p.Ile41Val), rs1563584220, ClinGen CA371663114, ClinVar RCV001057800, ClinVar RCV001182851, REVEL 0.15, CADD 19.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- R43* (p.Arg43Ter), rs200287925, ClinGen CA167743, ClinVar RCV000131193, ClinVar RCV000409406, CADD 35.00, Pathogenic
- R43G (p.Arg43Gly), rs200287925, ClinGen CA371663057, ClinVar RCV002385275, Uncertain significance, Hereditary cancer-predisposing syndrome
- R43L (p.Arg43Leu), rs759146120, ClinGen CA371663045, ClinVar RCV001235839, ClinVar RCV005372612, AlphaMissense 0.96, MetaLR 0.41, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- R43Q (p.Arg43Gln), rs759146120, ClinGen CA4803053, NCI-TCGA Cosmic COSV5537, ClinVar RCV000567458, REVEL 0.45, AlphaMissense 0.96, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- N44S (p.Asn44Ser), rs2488368719, ClinGen CA371663039, ClinVar RCV003341869, Uncertain significance, Hereditary cancer-predisposing syndrome
- H45D (p.His45Asp), rs773865323, ClinGen CA371663033, ClinVar RCV000527832, ClinVar RCV000777185, REVEL 0.91, CADD 27.40, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- H45Q (p.His45Gln), rs770618624, ClinGen CA371663023, ClinVar RCV001901292, ClinVar RCV002482751, REVEL 0.91, CADD 23.90, Uncertain significance, Aplastic anemia; Microcephaly, normal intelligence and immunodeficiency; Acute l
- H45R (p.His45Arg), rs1554569059, ClinGen CA371663027, ClinVar RCV000540420, gnomAD rs1554569059, REVEL 0.92, CADD 26.00, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- H45Y (p.His45Tyr), rs773865323, ClinGen CA4803052, ClinVar RCV002259247, ClinVar RCV003101425, REVEL 0.91, CADD 26.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- A46P (p.Ala46Pro), rs1812129847, ClinGen CA371663017, ClinVar RCV001929450, ClinVar RCV002386748, REVEL 0.59, CADD 26.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- A46S (p.Ala46Ser), TOPMed rs1812129847, gnomAD rs1812129847, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- A46T (p.Ala46Thr), TOPMed rs1812129847, gnomAD rs1812129847, Uncertain significance
- A46V (p.Ala46Val), Ensembl rs2129924605
- V47L (p.Val47Leu), rs876658446, ClinGen CA10578811, ClinVar RCV000213612, ClinVar RCV005090078, AlphaMissense 0.15, MetaLR 0.43, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- V47M (p.Val47Met), rs876658446, ClinGen CA371663010, ClinVar RCV000564780, ClinVar RCV001354454, REVEL 0.34, AlphaMissense 0.15, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- L48* (p.Leu48Ter), rs2129924518, ClinGen CA371662994, ClinVar RCV001959178, Ensembl rs2129924518, Pathogenic
- L48S (p.Leu48Ser), rs2129924518, ClinGen CA371662996, ClinVar RCV003618142, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- T49I (p.Thr49Ile), rs1450189149, ClinGen CA371662985, ClinVar RCV001863627, gnomAD rs1450189149, REVEL 0.05, CADD 23.00, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- T49P (p.Thr49Pro), rs1064794807, ClinGen CA16618717, ClinVar RCV000485569, ClinVar RCV005443077, REVEL 0.33, CADD 24.80, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome
- A50T (p.Ala50Thr), Ensembl rs2129924411, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- A50V (p.Ala50Val), rs1554569035, ClinGen CA371662979, ClinVar RCV000636752, ClinVar RCV001011910, AlphaMissense 0.12, MetaLR 0.19, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- N51D (p.Asn51Asp), rs2488368446, ClinGen CA371662977, ClinVar RCV003003224, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- N51K (p.Asn51Lys), rs876661214, gnomAD rs876661214, ClinGen CA10577370, ClinVar RCV000222963, REVEL 0.21, CADD 21.30, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- F52L (p.Phe52Leu), ExAC rs777925415, gnomAD rs777925415, Likely benign
- F52Y (p.Phe52Tyr), Ensembl rs1812128449, REVEL 0.10, CADD 21.50
- S53C (p.Ser53Cys), rs876660243, ClinGen CA371662928, ClinVar RCV001763973, ClinVar RCV001885048, REVEL 0.50, CADD 28.10, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Microcephaly, normal inte
- S53F (p.Ser53Phe), rs876660243, ClinGen CA10578809, ClinVar RCV000220179, Ensembl rs876660243, REVEL 0.52, CADD 29.50, Uncertain significance, Hereditary cancer-predisposing syndrome
- V54A (p.Val54Ala), rs769700749, ClinGen CA371662913, ClinVar RCV001306333, ExAC rs769700749, AlphaMissense 0.10, MetaLR 0.16, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- V54E (p.Val54Glu), ExAC rs769700749, gnomAD rs769700749, Uncertain significance
- V54I (p.Val54Ile), rs1211487080, ClinGen CA371662916, ClinVar RCV001030568, TOPMed rs1211487080, AlphaMissense 0.08, MetaLR 0.18, Uncertain significance, Hereditary breast ovarian cancer syndrome
- T55S (p.Thr55Ser), rs1812127566, ClinGen CA371662901, ClinVar RCV001036960, Ensembl rs1812127566, AlphaMissense 0.09, MetaLR 0.21, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- N56K (p.Asn56Lys), rs1586111516, ClinGen CA371662872, ClinVar RCV003341868, ClinGen CA371662876, AlphaMissense 0.17, MetaLR 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome
- N56S (p.Asn56Ser), rs1554569009, ClinGen CA371662880, ClinVar RCV000636725, ClinVar RCV002248838, AlphaMissense 0.06, MetaLR 0.18, Uncertain significance, not specified; Hereditary cancer-predisposing syndrome; Microcephaly, normal int
- L57P (p.Leu57Pro), rs747920256, ClinGen CA4803045, ClinVar RCV000583436, ClinVar RCV000636739, REVEL 0.19, CADD 21.00, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- L57V (p.Leu57Val), rs1586111504, ClinGen CA371662869, ClinVar RCV002511193, Uncertain significance, not provided
- S58C (p.Ser58Cys), rs1554568431, ClinGen CA371662646, ClinVar RCV000568176, ClinVar RCV003617823, AlphaMissense 0.09, MetaLR 0.57, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- S58N (p.Ser58Asn), rs1586109204, ClinGen CA371662645, ClinVar RCV001012939, Ensembl rs1586109204, AlphaMissense 0.11, MetaLR 0.46, Uncertain significance, Hereditary cancer-predisposing syndrome
- S58R (p.Ser58Arg), gnomAD rs1381256979, Likely benign
- Q59* (p.Gln59Ter), rs1554568427, ClinGen CA371662638, ClinVar RCV000586448, ClinVar RCV000688264, AlphaMissense 0.07, MetaLR 0.48, Pathogenic
- Q59E (p.Gln59Glu), rs1554568427, ClinGen CA371662639, ClinVar RCV001911649, ClinVar RCV002511110, REVEL 0.35, AlphaMissense 0.07, Uncertain significance, not provided; Microcephaly, normal intelligence and immunodeficiency
- Q59R (p.Gln59Arg), rs2488361714, ClinGen CA371662637, ClinVar RCV003306708, Uncertain significance, Hereditary cancer-predisposing syndrome
- T60I (p.Thr60Ile), Ensembl rs1586109164, Benign
- T60K (p.Thr60Lys), rs1586109164, ClinGen CA371662629, ClinVar RCV001013218, ClinVar RCV002249631, REVEL 0.25, AlphaMissense 0.09, Conflicting interpretations, Aplastic anemia; Hereditary cancer-predisposing syndrome; not specified
- T60R (p.Thr60Arg), rs1586109164, ClinGen CA371662628, ClinVar RCV002407844, AlphaMissense 0.09, MetaLR 0.43, Uncertain significance, Hereditary cancer-predisposing syndrome
- D61G (p.Asp61Gly), rs1460282206, ClinGen CA371662623, ClinVar RCV000772939, ClinVar RCV001056239, REVEL 0.04, CADD 18.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- D61H (p.Asp61His), rs1812067648, ClinGen CA371662625, ClinVar RCV002735152, ClinVar RCV004067701, AlphaMissense 0.07, MetaLR 0.04, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- D61N (p.Asp61Asn), rs1812067648, ClinGen CA371662626, ClinVar RCV003619008, ClinVar RCV005240900, AlphaMissense 0.07, MetaLR 0.04, Uncertain significance, not specified; Microcephaly, normal intelligence and immunodeficiency
- E62* (p.Glu62Ter), NCI-TCGA TCGA novel, CADD 39.00, Variant assessed as somatic; high impact.
- E62D (p.Glu62Asp), rs1586109110, ClinGen CA371662612, ClinVar RCV000821079, Ensembl rs1586109110, AlphaMissense 0.11, MetaLR 0.11, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- E62G (p.Glu62Gly), Ensembl rs1812067152, Uncertain significance
- E62K (p.Glu62Lys), rs2488361617, ClinGen CA371662618, ClinVar RCV004513829, Uncertain significance, Hereditary cancer-predisposing syndrome
- E62V (p.Glu62Val), rs1812067152, ClinGen CA371662613, ClinVar RCV001911600, ClinVar RCV002407030, AlphaMissense 0.11, MetaLR 0.10, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- I63N (p.Ile63Asn), rs961554359, ClinGen CA181280638, ClinVar RCV000698049, ClinVar RCV000772344, AlphaMissense 0.13, MetaLR 0.35, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- P64A (p.Pro64Ala), rs267602038, ClinGen CA371662603, ClinVar RCV001901893, ExAC rs267602038, AlphaMissense 0.29, MetaLR 0.71, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- P64L (p.Pro64Leu), rs1563581492, ClinGen CA371662600, ClinVar RCV000772229, ClinVar RCV001217448, REVEL 0.70, CADD 31.00, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency; Hereditary cancer-predis
- P64R (p.Pro64Arg), rs1563581492, ClinGen CA371662601, ClinVar RCV000688507, ClinVar RCV001805805, REVEL 0.76, CADD 28.60, Uncertain significance, Hereditary cancer-predisposing syndrome; Aplastic anemia; Microcephaly, normal i
- P64S (p.Pro64Ser), rs267602038, ClinGen CA4803023, ClinVar RCV000670697, ClinVar RCV001013653, REVEL 0.50, AlphaMissense 0.29, Uncertain significance, Aplastic anemia; Hereditary cancer-predisposing syndrome; Microcephaly, normal i
- P64T (p.Pro64Thr), rs267602038, ClinGen CA371662604, ClinVar RCV004513831, ExAC rs267602038, REVEL 0.61, AlphaMissense 0.29, Uncertain significance, Hereditary cancer-predisposing syndrome
- V65E (p.Val65Glu), rs1563581457, ClinGen CA371662597, ClinVar RCV000700707, ClinVar RCV002422565, AlphaMissense 0.13, MetaLR 0.43, Uncertain significance, Aplastic anemia; Microcephaly, normal intelligence and immunodeficiency; Heredit
- V65I (p.Val65Ile), rs778998026, ClinGen CA4803022, ClinVar RCV000565097, ClinVar RCV001039847, REVEL 0.24, AlphaMissense 0.09, Conflicting interpretations, not specified; Hereditary cancer-predisposing syndrome; Microcephaly, normal int
- V65L (p.Val65Leu), rs778998026, ClinGen CA371662598, ClinVar RCV001322027, ExAC rs778998026, AlphaMissense 0.09, MetaLR 0.48, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- L66F (p.Leu66Phe), ExAC rs757735005, gnomAD rs757735005, REVEL 0.79, CADD 24.80, Likely benign
- L66V (p.Leu66Val), rs1554568371, ClinGen CA371662593, ClinVar RCV000574071, Ensembl rs1554568371, AlphaMissense 0.14, MetaLR 0.55, Uncertain significance, Hereditary cancer-predisposing syndrome
- L66W (p.Leu66Trp), rs1812065476, ClinGen CA371662590, ClinVar RCV001047145, Ensembl rs1812065476, AlphaMissense 0.95, MetaLR 0.69, Uncertain significance, Microcephaly, normal intelligence and immunodeficiency
- T67A (p.Thr67Ala), rs876660922, ClinGen CA10578807, ClinVar RCV000220748, ClinVar RCV000636750, AlphaMissense 0.13, MetaLR 0.16, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
- T67I (p.Thr67Ile), rs1015793589, ClinGen CA181280618, ClinVar RCV000813374, ClinVar RCV002422804, AlphaMissense 0.11, MetaLR 0.15, Uncertain significance, Hereditary cancer-predisposing syndrome; Microcephaly, normal intelligence and i
Public NBN analysis runs
- NBN analysis run — NBN (2,307 variants) — completed 2026-08-18