Table 3 Summary of method features
Model # | Team | Variant call quality | Variant allele frequency | Variant deleteriousness prediction | Familial segregation | Relevance to phenotype | Limited to human disease-associated genes | Limited to coding regions | Submitted compound heterozygous variants |
|---|---|---|---|---|---|---|---|---|---|
1 | Team 9 (Invitae Moon) | Yes | Yes—≤ 2% gnomAD, plus more common P/LP variants | Yes—trained on ClinVar and in-house classifications | Yes—plus incomplete penetrance | Yes | Yes—Apollo database | Yes—plus known P/LP non-coding variants | Yes |
1 | Team 12 (Lichtarge) | Yes | Yes | Yes—Evolutionary Action | Yes | Yes | Yes—HPO, DisGeNet, ClinVar, HumSavar, literature | Yes—frameshift, nonsense, and missense only (excluded causal variant in P19) | Yes |
2–3 | Team 12 (Lichtarge) | Yes | Yes | Yes—Evolutionary Action | Yes | Yes | Yes—VarElect NGS Phenotyper | Yes—frameshift, nonsense, and missense only (excluded causal variant in P19) | Yes |
1–4 | Team 11 (enGenome) | Yes | Yes | Yes | Yes | Yes | Yes—MedGen, Disease Ontology, Orphanet (excluded causal variants in P6 and P23) | No | Yes |
1–3 | Team 14 (TCS) | Yes | Yes | Yes (excluded causal variant in P16) | Yes (variant in P5 was predicted as compound heterozygous with another variant) | Yes | Yes—ClinVar, HPO, STRING, PubMed (excluded causal variant in P6) | Yes | Yes |
1 | Team 5 (Exomiser) | Yes | Yes—< 0.1% dominant, < 2% cmphet recessive 1000 Genomes, ExAC, gnomAD | Yes—REVEL, MVP (excluded causal variant in P24) | Yes—did not allow for sex-limited expression (excluded causal variant in P27) | Yes | No—also included model organisms and interacting proteins | Yes—plus known P/LP non-coding variants | Yes |
2 | Team 5 (Exomiser) | Yes | Yes—< 0.1% dominant, < 2% cmphet recessive 1000 Genomes, ExAC, gnomAD | Yes—REVEL, MVP (excluded causal variant in P24) | Yes—did not allow for sex-limited expression (excluded causal variant in P27) | Yes | Yes—OMIM, Orphanet (excluded causal variants in P6 and P23) | Yes—plus known P/LP non-coding variants | Yes |
3 | Team 5 (Exomiser) | No | Yes—< 0.1% dominant, < 2% cmphet recessive 1000 Genomes, ExAC, gnomAD | Yes—REVEL, MVP (excluded causal variant in P24) | Yes—did not allow for sex-limited expression (excluded causal variant in P27) | Yes | Yes—OMIM, Orphanet (excluded causal variants in P6 and P23) | Yes—plus known P/LP non-coding variants | Yes |
4 | Team 5 (Exomiser) | Yes | Yes—< 0.1% dominant, < 2% cmphet recessive 1000 Genomes, ExAC, gnomAD | Yes—REVEL, MVP (excluded causal variant in P24) | Yes—plus incomplete penetrance | Yes | Yes—OMIM, Orphanet (excluded causal variants in P6 and P23) | Yes—plus known P/LP non-coding variants | Yes |
5 | Team 5 (Exomiser) | No | Yes—< 0.1% dominant, < 2% cmphet recessive 1000 Genomes, ExAC, gnomAD | Yes—REVEL, MVP (excluded causal variant in P24) | Yes—did not allow for sex-limited expression (excluded causal variant in P27) | Yes | Yes—OMIM, Orphanet (excluded causal variants in P6 and P23) | No | Yes |
1–6 | Team 4 (DITTO) | Yes | No | Yes—trained on ClinVar and HGMD classifications | No | Yes—Exomiser | No | No | No (excluded causal variant in P5) |
1–6 | Team 2 (AIBI) | No | Yes—< 5% | Yes—REVEL | Yes | Yes—Phenolyzer | Yes—HPO | Yes | Yes |
1 | Team 13 | Yes | Yes—< 0.1% | Yes—MutPred2 (excluded causal variant in P27) | Yes—absent in parent if data avaliable (excluded causal variants in P5 and P27) | Yes—HPO including interacting proteins | No | Yes—missense only (excluded causal variants in P5, P7, P16, P19, and P22) | No (excluded causal variant in P5) |
2 | Team 13 | Yes | Yes—< 0.1% | Yes—REVEL (excluded causal variant in P27) | Yes—absent in parent if data available (excluded causal variants in P5 and P27) | Yes—HPO including interacting proteins | No | Yes—missense only (excluded causal variants in P5, P7, P16, P19, and P22) | No (excluded causal variant in P5) |
1–4 | Team 8 (BORG) | Yes | Yes—≤ 1% 1000 Genomes, ExAC, gnomAD | Yes—CADD | Yes | Yes—HPO | - | - | No (excluded causal variant in P5) |
1 | Team 7 (Uniss) | – | Yes—≤ 1% gnomAD | Yes | - | Yes—HPO, Orphanet | Yes | - | No (excluded causal variant in P5) |
1 | Team 3 (Bologna Biocomputing Group) | – | Yes—≤ 1% gnomAD | - | Yes | Yes—eDGAR, PhenPath (excluded causal variants in P4, P7, and P21) | Yes—eDGAR, PhenPath | Yes—frameshift, nonsense, and missense only (excluded causal variant in P19) | No (excluded causal variant in P5) |
2 | Team 3 (Bologna Biocomputing Group) | – | Yes—≤ 1% gnomAD | - | Yes—de novo and homozygous only (excluded causal variants in P2, P5, P6, P11, P22, and P27) | Yes—eDGAR, PhenPath (excluded causal variants in P4, P7, and P21) | No | Yes—frameshift, nonsense, and missense only (excluded causal variant in P19) | No (excluded causal variant in P5) |