SHANK2 (Q9UPX8) variants and mutations
SHANK2 (also known as Q9UPX8) is a human protein-coding gene encoding a SH3 and multiple ankyrin repeat domains protein 2 protein. It scaffolds receptors, signaling proteins, and actin-regulatory complexes within excitatory postsynaptic densities. Haploinsufficiency and disruptive variants can contribute to neurodevelopmental disorders, including intellectual disability and autism spectrum phenotypes. This analysis covers 2,783 SHANK2 variants and mutations. Of these, 69% have computational variant effect predictions. Disease context includes complex neurodevelopmental disorder, autism, and Rare disease with autism. Example SHANK2 variants include P2L, P2T, and R3C.
Variant analysis overview
- Gene: SHANK2
- Protein: Q9UPX8
- UniProt accession: Q9UPX8
- Organism: Homo sapiens
- Variants analyzed: 2783
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 2,425 unspecified-consequence records; 2 stop retained variant; 179 missense variants; 161 synonymous variants; 3 stop-gained variants; 5 in-frame deletions; 4 frameshift variants; 3 stop lost; 1 splice-region variants
- Prediction scores: 1,917 variants have prediction scores (69% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: complex neurodevelopmental disorder, autism, Rare disease with autism, autism spectrum disorder, Intellectual disability, diabetic ketoacidosis, alcohol drinking, Hodgkins lymphoma, neurodevelopmental disorder, Global developmental delay, Abnormality of the skeletal system, bipolar disorder.
Protein structure and variant hotspots
- Protein features: 3 domains; 8 post-translational modification sites.
- Structural context: 297 variants have structural context.
- PTM context: 17 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable SHANK2 variants
Examples include P2L, P2T, R3C, R3H, R3L, S4G, T6A, S8G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), rs115978536, ClinGen CA6162194, ClinVar RCV004540921, 1000Genomes rs115978536, CADD 24.00, PolyPhen-2 0.97, Benign, SHANK2-related disorder
- P2T (p.Pro2Thr), TOPMed rs1190471594, gnomAD rs1190471594, CADD 20.30, PolyPhen-2 0.91
- R3C (p.Arg3Cys), rs373379917, ClinGen CA6162193, ClinVar RCV002520760, 1000Genomes rs373379917, CADD 23.00, PolyPhen-2 0.03, Likely benign, Inborn genetic diseases
- R3H (p.Arg3His), rs369450251, ClinGen CA6162192, ClinVar RCV003398104, 1000Genomes rs369450251, CADD 19.30, PolyPhen-2 0.81, Likely benign, not provided
- R3L (p.Arg3Leu), rs369450251, ClinGen CA381961542, cosmic curated COSV99064, ClinVar RCV003441488, CADD 20.60, PolyPhen-2 0.37, Uncertain significance, not provided; not specified
- S4G (p.Ser4Gly), Ensembl rs2135405046
- T6A (p.Thr6Ala), gnomAD rs1555106924, CADD 19.20, PolyPhen-2 0.99
- S8G (p.Ser8Gly), Ensembl rs2135405015, CADD 24.00, PolyPhen-2 0.99
- S8I (p.Ser8Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E9K (p.Glu9Lys), 1000Genomes rs558310216, ExAC rs558310216, gnomAD rs558310216, CADD 24.40, PolyPhen-2 0.99
- D10E (p.Asp10Glu), TOPMed rs1325712787, gnomAD rs1325712787, CADD 15.90, PolyPhen-2 0.20
- D10N (p.Asp10Asn), TOPMed rs1555106917, gnomAD rs1555106917, CADD 24.90, PolyPhen-2 0.91, Uncertain significance, Inborn genetic diseases
- E11D (p.Glu11Asp), cosmic curated COSV58346
- E11K (p.Glu11Lys), TOPMed rs1369198408, gnomAD rs1369198408, CADD 24.70, PolyPhen-2 0.56
- M12T (p.Met12Thr), TOPMed rs1443512753, gnomAD rs1443512753, CADD 17.10, PolyPhen-2 0.09
- A13S (p.Ala13Ser), NCI-TCGA Cosmic COSV5834, cosmic curated COSV58345, Ensembl rs1952673460, CADD 23.00, PolyPhen-2 1.00, Variant assessed as somatic; moderate impact.
- A13V (p.Ala13Val), TOPMed rs1952673400, gnomAD rs1952673400, CADD 24.10, PolyPhen-2 1.00
- Q14* (p.Gln14Ter), gnomAD rs1555106911, CADD 40.00
- F16L (p.Phe16Leu), gnomAD rs1555106908, CADD 21.10, PolyPhen-2 0.00
- S17F (p.Ser17Phe), NCI-TCGA TCGA novel, Ensembl rs1952673100, CADD 26.50, PolyPhen-2 1.00, Variant assessed as somatic; moderate impact.
- D18N (p.Asp18Asn), rs1308508787, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10063, NCI-TCGA Cosmic COSV5832, CADD 22.60, PolyPhen-2 0.42, Variant assessed as somatic; moderate impact.
- D18Y (p.Asp18Tyr), cosmic curated COSV58324, TOPMed rs1308508787, gnomAD rs1308508787
- S20Y (p.Ser20Tyr), ESP rs373335096, ExAC rs373335096, TOPMed rs373335096, gnomAD rs373335096, CADD 25.50, PolyPhen-2 0.98, Uncertain significance, Inborn genetic diseases
- V21L (p.Val21Leu), NCI-TCGA TCGA novel, CADD 7.76, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- V21M (p.Val21Met), rs782574580, ClinGen CA6162185, ClinVar RCV003273007, ExAC rs782574580, CADD 10.10, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases
- G22A (p.Gly22Ala), TOPMed rs1214032004, gnomAD rs1214032004, CADD 22.20
- G22E (p.Gly22Glu), TOPMed rs1214032004, gnomAD rs1214032004, CADD 17.90, PolyPhen-2 0.00
- G22R (p.Gly22Arg), TOPMed rs1555106901, gnomAD rs1555106901, CADD 23.40, PolyPhen-2 0.23
- S23L (p.Ser23Leu), rs782481305, NCI-TCGA Cosmic COSV5835, cosmic curated COSV58353, ExAC rs782481305, CADD 25.30, PolyPhen-2 0.46, Variant assessed as somatic; moderate impact.
- E24* (p.Glu24Ter), cosmic curated COSV58336
- E24D (p.Glu24Asp), TOPMed rs1952671752, CADD 15.90, PolyPhen-2 0.00
- S25L (p.Ser25Leu), ExAC rs781832716
- D26Y (p.Asp26Tyr), cosmic curated COSV10591
- S28C (p.Ser28Cys), TOPMed rs1175615216, gnomAD rs1175615216, CADD 23.80, PolyPhen-2 0.03
- E30* (p.Glu30Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- T32S (p.Thr32Ser), TOPMed rs1420248139, gnomAD rs1420248139, CADD 18.60, PolyPhen-2 0.01
- I33L (p.Ile33Leu), gnomAD rs1555106895, CADD 18.00, PolyPhen-2 0.02
- I33M (p.Ile33Met), TOPMed rs1392856209, gnomAD rs1392856209, CADD 19.30, PolyPhen-2 0.37
- Y34C (p.Tyr34Cys), cosmic curated COSV58349, Ensembl rs1952671166, CADD 23.70, PolyPhen-2 1.00
- Y34D (p.Tyr34Asp), Ensembl rs1952671240
- D35A (p.Asp35Ala), TOPMed rs1463356059
- T36M (p.Thr36Met), rs782758703, ExAC rs782758703, TOPMed rs782758703, gnomAD rs782758703, CADD 23.20, PolyPhen-2 0.34, Variant assessed as somatic; moderate impact.
- R38L (p.Arg38Leu), cosmic curated COSV58317
- R38Q (p.Arg38Gln), rs1280829265, ClinGen CA381961285, ClinVar RCV003347552, TOPMed rs1280829265, CADD 23.70, PolyPhen-2 0.90, Conflicting interpretations, not provided; Inborn genetic diseases
- R38W (p.Arg38Trp), rs369954613, ClinGen CA6162181, ClinVar RCV002692512, ESP rs369954613, CADD 26.10, PolyPhen-2 0.99, Uncertain significance, Inborn genetic diseases
- A39V (p.Ala39Val), gnomAD rs1555106884, CADD 23.80, PolyPhen-2 0.32
- A41V (p.Ala41Val), 1000Genomes rs566259872, ExAC rs566259872, TOPMed rs566259872, gnomAD rs566259872, CADD 20.90, PolyPhen-2 0.12
- E42D (p.Glu42Asp), ExAC rs782805943, gnomAD rs782805943
- K43* (p.Lys43Ter), cosmic curated COSV58347, gnomAD rs1555106882, CADD 37.00
- P44L (p.Pro44Leu), rs554208670, ClinGen CA6162178, cosmic curated COSV10063, ClinVar RCV000449618, CADD 23.80, PolyPhen-2 0.69, Uncertain significance, Intellectual disability; Inborn genetic diseases
- G45S (p.Gly45Ser), TOPMed rs1233748147, gnomAD rs1233748147, CADD 13.10
- G46S (p.Gly46Ser), rs201642016, ClinGen CA6162175, ClinVar RCV002520759, ClinVar RCV005411409, CADD 0.85, PolyPhen-2 0.00, Likely benign, not provided; Inborn genetic diseases; Intellectual disability
- A47T (p.Ala47Thr), gnomAD rs1555106876, CADD 18.80
- R48G (p.Arg48Gly), gnomAD rs1555106873, CADD 14.30, PolyPhen-2 0.04, Uncertain significance, Inborn genetic diseases
- T49M (p.Thr49Met), rs782002202, NCI-TCGA Cosmic COSV5832, cosmic curated COSV58325, ExAC rs782002202, CADD 0.12, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- E51D (p.Glu51Asp), gnomAD rs1555106864, CADD 13.70, PolyPhen-2 0.00
- Q53F (p.Gln53Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G54C (p.Gly54Cys), gnomAD rs1555106859, CADD 17.60, PolyPhen-2 0.33
- G54D (p.Gly54Asp), TOPMed rs1187236989, gnomAD rs1187236989, CADD 15.30, PolyPhen-2 0.04
- G54S (p.Gly54Ser), gnomAD rs1555106859
- G54V (p.Gly54Val), cosmic curated COSV58317, CADD 13.60, PolyPhen-2 0.01
- N55D (p.Asn55Asp), ExAC rs782296061, TOPMed rs782296061, gnomAD rs782296061, CADD 14.30, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases
- N55H (p.Asn55His), ExAC rs782296061, TOPMed rs782296061, gnomAD rs782296061, CADD 13.60, PolyPhen-2 0.00
- N55S (p.Asn55Ser), rs781924055, ClinGen CA6162171, ClinVar RCV002704678, ExAC rs781924055, CADD 17.90, PolyPhen-2 0.00, Likely benign, Inborn genetic diseases
- N55T (p.Asn55Thr), ExAC rs781924055, TOPMed rs781924055, gnomAD rs781924055, Likely benign
- T56K (p.Thr56Lys), ExAC rs782325822, TOPMed rs782325822, gnomAD rs782325822, CADD 22.70, PolyPhen-2 0.10
- T56M (p.Thr56Met), ExAC rs782325822, TOPMed rs782325822, gnomAD rs782325822, CADD 17.20, PolyPhen-2 0.01, Likely benign, not provided
- L57P (p.Leu57Pro), TOPMed rs1952668301, CADD 26.70, PolyPhen-2 0.76
- R60C (p.Arg60Cys), cosmic curated COSV58347, ExAC rs782623478, TOPMed rs782623478, gnomAD rs782623478, CADD 26.30, PolyPhen-2 0.95
- R60H (p.Arg60His), 1000Genomes rs782494595, ExAC rs782494595, TOPMed rs782494595, gnomAD rs782494595, CADD 23.40, PolyPhen-2 0.20
- V61M (p.Val61Met), cosmic curated COSV10063, TOPMed rs1413638609, gnomAD rs1413638609, CADD 21.00, PolyPhen-2 0.32
- V62F (p.Val62Phe), TOPMed rs1555106842, gnomAD rs1555106842, CADD 4.66, PolyPhen-2 0.00
- I63M (p.Ile63Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I63T (p.Ile63Thr), Ensembl rs1952667636
- H64P (p.His64Pro), 1000Genomes rs200995537, ESP rs200995537, ExAC rs200995537, TOPMed rs200995537, CADD 19.00, Uncertain significance
- H64R (p.His64Arg), 1000Genomes rs200995537, ESP rs200995537, ExAC rs200995537, TOPMed rs200995537, CADD 23.20, PolyPhen-2 0.01, Uncertain significance
- D65V (p.Asp65Val), TOPMed rs1555106839, gnomAD rs1555106839, CADD 27.70, PolyPhen-2 1.00
- Q67* (p.Gln67Ter), NCI-TCGA TCGA novel, CADD 44.00, Variant assessed as somatic; high impact.
- Q67H (p.Gln67His), TOPMed rs1357357893, gnomAD rs1357357893, CADD 22.70, PolyPhen-2 0.99
- Q67K (p.Gln67Lys), ExAC rs782661932, gnomAD rs782661932, CADD 23.40, PolyPhen-2 0.97
- Q68* (p.Gln68Ter), Ensembl rs1952667159
- T69M (p.Thr69Met), cosmic curated COSV58327, ExAC rs782547223, TOPMed rs782547223, gnomAD rs782547223, CADD 26.20, PolyPhen-2 0.67, Likely benign, Inborn genetic diseases
- C71F (p.Cys71Phe), 1000Genomes rs182549877, ExAC rs182549877, TOPMed rs182549877, gnomAD rs182549877
- C71R (p.Cys71Arg), Ensembl rs1565461848, CADD 25.90, PolyPhen-2 0.84
- C71Y (p.Cys71Tyr), 1000Genomes rs182549877, ExAC rs182549877, TOPMed rs182549877, gnomAD rs182549877, CADD 25.00, PolyPhen-2 0.91
- I72F (p.Ile72Phe), 1000Genomes rs568434832, TOPMed rs568434832, gnomAD rs568434832, CADD 22.60, PolyPhen-2 0.41
- I72T (p.Ile72Thr), TOPMed rs1483304922
- I72V (p.Ile72Val), cosmic curated COSV10063, 1000Genomes rs568434832, TOPMed rs568434832, gnomAD rs568434832, CADD 20.50, PolyPhen-2 0.09
- R73* (p.Arg73Ter), cosmic curated COSV58339, ExAC rs782146308, gnomAD rs782146308, CADD 38.00
- R73L (p.Arg73Leu), TOPMed rs1555100977, gnomAD rs1555100977, CADD 26.10, PolyPhen-2 0.99, Uncertain significance
- R73P (p.Arg73Pro), rs1555100977, ClinGen CA381960223, ClinVar RCV002832224, TOPMed rs1555100977, CADD 26.20, PolyPhen-2 1.00, Uncertain significance, Inborn genetic diseases
- R73Q (p.Arg73Gln), cosmic curated COSV10591, TOPMed rs1555100977, gnomAD rs1555100977, CADD 24.10, PolyPhen-2 0.99, Uncertain significance, Inborn genetic diseases
- P76L (p.Pro76Leu), rs199717803, ClinGen CA6162157, cosmic curated COSV10465, ClinVar RCV001090418, CADD 23.70, PolyPhen-2 1.00, Conflicting interpretations, not provided; Autism, susceptibility to, 17; Inborn genetic diseases
- P76T (p.Pro76Thr), TOPMed rs1555100974, gnomAD rs1555100974, CADD 24.10, PolyPhen-2 1.00
- D77N (p.Asp77Asn), TOPMed rs1555100969, gnomAD rs1555100969, CADD 19.40, PolyPhen-2 0.43
- A78G (p.Ala78Gly), rs2502057730, ClinGen CA381960188, ClinVar RCV002718799, Uncertain significance, Inborn genetic diseases
- A78T (p.Ala78Thr), Ensembl rs1952033977, CADD 23.50, PolyPhen-2 0.99
- T79I (p.Thr79Ile), rs2502057697, ClinGen CA381960181, ClinVar RCV003443421, CADD 23.80, PolyPhen-2 0.63, Uncertain significance, not provided
- W81* (p.Trp81Ter), TOPMed rs1164911385, gnomAD rs1164911385, CADD 37.00
- A83S (p.Ala83Ser), rs2502057442, ClinGen CA381960157, ClinVar RCV004542631, Uncertain significance, SHANK2-related disorder
- K84E (p.Lys84Glu), Ensembl rs1952033530
- Q85* (p.Gln85Ter), cosmic curated COSV58329
- R86Q (p.Arg86Gln), cosmic curated COSV58328, TOPMed rs1555100962, gnomAD rs1555100962, CADD 9.12, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases
- R86W (p.Arg86Trp), ESP rs377135249, ExAC rs377135249, TOPMed rs377135249, gnomAD rs377135249, CADD 23.30, PolyPhen-2 0.85, Uncertain significance, Inborn genetic diseases
- C89Y (p.Cys89Tyr), 1000Genomes rs530759559, ExAC rs530759559, gnomAD rs530759559, CADD 23.50
- T90A (p.Thr90Ala), cosmic curated COSV10063
- T90I (p.Thr90Ile), rs1167034682, ClinGen CA381960107, ClinVar RCV004450883, TOPMed rs1167034682, CADD 23.00, PolyPhen-2 0.60, Uncertain significance, Inborn genetic diseases
- T92I (p.Thr92Ile), cosmic curated COSV58322, Ensembl rs1952033146
- Q93* (p.Gln93Ter), rs1555100954, ClinGen CA381960091, ClinVar RCV000622565, ClinVar RCV003488732, CADD 37.00, Likely pathogenic
- Q93H (p.Gln93His), 1000Genomes rs563452320, ExAC rs563452320, gnomAD rs563452320, CADD 19.50, PolyPhen-2 0.99
- L95* (p.Leu95Ter), cosmic curated COSV10465
- K96Q (p.Lys96Gln), TOPMed rs1410894995
- N100T (p.Asn100Thr), gnomAD rs1555100949, CADD 24.90, PolyPhen-2 0.99
- Y101* (p.Tyr101Ter), ExAC rs782404066, TOPMed rs782404066, gnomAD rs782404066
- Y101C (p.Tyr101Cys), gnomAD rs1555100948, CADD 25.90, PolyPhen-2 0.99
- G102S (p.Gly102Ser), TOPMed rs1377679556, gnomAD rs1377679556, CADD 25.00, PolyPhen-2 1.00
- L103P (p.Leu103Pro), TOPMed rs1313562822, gnomAD rs1313562822, CADD 26.40, PolyPhen-2 1.00
- Q105* (p.Gln105Ter), cosmic curated COSV10465
- Q105H (p.Gln105His), TOPMed rs1277123294, CADD 23.50, PolyPhen-2 0.99
- Q105P (p.Gln105Pro), ExAC rs782285873, TOPMed rs782285873, gnomAD rs782285873, CADD 25.40, PolyPhen-2 0.99
- Q105R (p.Gln105Arg), ExAC rs782285873, TOPMed rs782285873, gnomAD rs782285873, CADD 25.10, PolyPhen-2 0.98
- P106L (p.Pro106Leu), 1000Genomes rs545370532, ExAC rs545370532, TOPMed rs545370532, gnomAD rs545370532, CADD 25.90, PolyPhen-2 1.00
- P106Q (p.Pro106Gln), 1000Genomes rs545370532, ExAC rs545370532, TOPMed rs545370532, gnomAD rs545370532
- P106R (p.Pro106Arg), 1000Genomes rs545370532, ExAC rs545370532, TOPMed rs545370532, gnomAD rs545370532, CADD 25.50
- A107D (p.Ala107Asp), gnomAD rs201921126, CADD 25.20, PolyPhen-2 0.96, Uncertain significance, Inborn genetic diseases
- A107S (p.Ala107Ser), gnomAD rs1555100934, CADD 22.20, PolyPhen-2 0.41
- A107V (p.Ala107Val), cosmic curated COSV58323, CADD 25.30, PolyPhen-2 0.96
- S108R (p.Ser108Arg), TOPMed rs1952032185, CADD 17.20, PolyPhen-2 0.22, Uncertain significance, not provided
- N109S (p.Asn109Ser), TOPMed rs1235633860, CADD 11.20, PolyPhen-2 0.06
- R111C (p.Arg111Cys), rs1484212852, NCI-TCGA Cosmic COSV5835, cosmic curated COSV58354, TOPMed rs1484212852, CADD 25.00, PolyPhen-2 1.00, Variant assessed as somatic; moderate impact.
- R111H (p.Arg111His), rs368652424, ClinGen CA6162146, cosmic curated COSV10063, ClinVar RCV002520758, CADD 22.80, PolyPhen-2 1.00, Likely benign, Inborn genetic diseases; not provided
- D112N (p.Asp112Asn), TOPMed rs1447212040, gnomAD rs1447212040, CADD 19.60, PolyPhen-2 0.18, Uncertain significance, Intellectual disability
- G113D (p.Gly113Asp), cosmic curated COSV58345, CADD 28.40, PolyPhen-2 0.94
- G113S (p.Gly113Ser), ExAC rs782517914, TOPMed rs782517914, gnomAD rs782517914, CADD 24.50, PolyPhen-2 0.45
- D117N (p.Asp117Asn), Ensembl rs1555100911, CADD 25.00, PolyPhen-2 0.74
- E118A (p.Glu118Ala), gnomAD rs1555100909
- E118D (p.Glu118Asp), cosmic curated COSV58321, CADD 22.90, PolyPhen-2 0.99
- E119K (p.Glu119Lys), Ensembl rs370116281, CADD 25.50, PolyPhen-2 0.99
- R120Q (p.Arg120Gln), ExAC rs782338107, TOPMed rs782338107, gnomAD rs782338107, CADD 25.00, PolyPhen-2 0.90
- R120W (p.Arg120Trp), TOPMed rs372935127, gnomAD rs372935127, CADD 26.20, PolyPhen-2 0.98
- L122P (p.Leu122Pro), Ensembl rs1590930320, CADD 25.20, PolyPhen-2 0.98
- R123C (p.Arg123Cys), rs367713202, ClinGen CA6162141, ClinVar RCV002707863, ESP rs367713202, CADD 24.00, PolyPhen-2 0.74, Uncertain significance, Inborn genetic diseases
- R123H (p.Arg123His), 1000Genomes rs561592558, ExAC rs561592558, TOPMed rs561592558, gnomAD rs561592558, CADD 23.30, PolyPhen-2 0.67
- R123L (p.Arg123Leu), 1000Genomes rs561592558, ExAC rs561592558, TOPMed rs561592558, gnomAD rs561592558, CADD 21.20, PolyPhen-2 0.05
- E124K (p.Glu124Lys), TOPMed rs1300066048, gnomAD rs1300066048, CADD 24.10, PolyPhen-2 0.51
- Y125H (p.Tyr125His), cosmic curated COSV58320
- P126S (p.Pro126Ser), gnomAD rs1555100895, CADD 22.80, PolyPhen-2 1.00
- Q127E (p.Gln127Glu), TOPMed rs1366247172, gnomAD rs1366247172
- Q127K (p.Gln127Lys), TOPMed rs1366247172, gnomAD rs1366247172, CADD 17.80
- P128T (p.Pro128Thr), cosmic curated COSV10610
- V129M (p.Val129Met), rs73521173, ClinGen CA6162138, cosmic curated COSV58353, ClinVar RCV004703603, CADD 0.05, PolyPhen-2 0.01, Likely benign, not provided
- E131K (p.Glu131Lys), TOPMed rs1952030431
- G132C (p.Gly132Cys), TOPMed rs1313820918, gnomAD rs1313820918
- G132S (p.Gly132Ser), TOPMed rs1313820918, gnomAD rs1313820918, CADD 23.90, PolyPhen-2 0.71
- G132V (p.Gly132Val), gnomAD rs1555100880, CADD 22.90, PolyPhen-2 0.99
- V133F (p.Val133Phe), TOPMed rs1463147374, gnomAD rs1463147374, CADD 16.60, PolyPhen-2 0.36, Uncertain significance
- V133I (p.Val133Ile), TOPMed rs1463147374, gnomAD rs1463147374, CADD 8.66, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases
- S135F (p.Ser135Phe), cosmic curated COSV10524, CADD 24.00, PolyPhen-2 0.69
- S135T (p.Ser135Thr), rs1248219644, ClinGen CA381959814, ClinVar RCV003384690, TOPMed rs1248219644, CADD 19.90, PolyPhen-2 0.02, Uncertain significance, Inborn genetic diseases
- L136V (p.Leu136Val), gnomAD rs1555100873, CADD 23.10, PolyPhen-2 0.99
- E137Q (p.Glu137Gln), gnomAD rs1555100871, CADD 24.00, PolyPhen-2 0.99
- R139* (p.Arg139Ter), rs1205314621, ClinGen CA381962015, cosmic curated COSV58321, ClinVar RCV002292839, CADD 39.00, Uncertain significance
- R139Q (p.Arg139Gln), rs1951923525, ClinGen CA381962014, ClinVar RCV001090417, TOPMed rs1951923525, CADD 26.70, PolyPhen-2 0.99, Uncertain significance, not provided
- K141R (p.Lys141Arg), gnomAD rs1555099783, CADD 26.40, PolyPhen-2 0.99
- R143Q (p.Arg143Gln), cosmic curated COSV10943, TOPMed rs1212217694, gnomAD rs1212217694, CADD 26.70, PolyPhen-2 0.99
- R143W (p.Arg143Trp), cosmic curated COSV10816, TOPMed rs1468274204, gnomAD rs1468274204, CADD 28.70, PolyPhen-2 1.00, Conflicting interpretations, Autism, susceptibility to, 17; Inborn genetic diseases
- V144A (p.Val144Ala), 1000Genomes rs782270817, ExAC rs782270817, TOPMed rs782270817, gnomAD rs782270817, CADD 25.70, PolyPhen-2 0.88, Likely benign, not provided
- V144G (p.Val144Gly), 1000Genomes rs782270817, ExAC rs782270817, TOPMed rs782270817, gnomAD rs782270817, CADD 27.30, PolyPhen-2 0.96
- V144L (p.Val144Leu), ExAC rs782383078, TOPMed rs782383078, gnomAD rs782383078, CADD 22.80, PolyPhen-2 0.20, Uncertain significance, not provided
- V144M (p.Val144Met), ExAC rs782383078, TOPMed rs782383078, gnomAD rs782383078, CADD 24.80, PolyPhen-2 0.96
- Y145* (p.Tyr145Ter), cosmic curated COSV10648, ExAC rs782662688, TOPMed rs782662688, gnomAD rs782662688, CADD 34.00
- Y145C (p.Tyr145Cys), gnomAD rs1555099774, CADD 26.30, PolyPhen-2 1.00
- K146E (p.Lys146Glu), TOPMed rs1471210445, CADD 22.90, PolyPhen-2 0.05
- Q147K (p.Gln147Lys), cosmic curated COSV10648, ExAC rs201263152, gnomAD rs201263152, CADD 22.70, PolyPhen-2 0.10
- A148D (p.Ala148Asp), cosmic curated COSV58316
- A148V (p.Ala148Val), gnomAD rs1951922927, CADD 22.90, PolyPhen-2 0.01
- D151N (p.Asp151Asn), TOPMed rs967203648, gnomAD rs967203648, CADD 23.20, PolyPhen-2 0.07, Likely benign
- D151Y (p.Asp151Tyr), rs967203648, ClinGen CA16603361, ClinVar RCV000427775, ClinVar RCV005480363, CADD 25.50, PolyPhen-2 0.98, Uncertain significance, Inborn genetic diseases
- E152* (p.Glu152Ter), rs1555099768, ClinGen CA381961927, ClinVar RCV000523113, Ensembl rs1555099768, CADD 41.00, Uncertain significance
- Q154* (p.Gln154Ter), rs1327654017, ClinGen CA381961911, ClinVar RCV002221858, ClinVar RCV005861280, CADD 41.00, Likely pathogenic
Public SHANK2 analysis runs
- SHANK2 analysis run — SHANK2 (2,783 variants) — completed 2026-08-19