Table 2.
Validated variants and classification according to ACMG-SHERLOC criteria42.
| GENE | ID | CHANGE (HGVS) | rs ID | gnomAD† | PD‡ | CL§ |
|---|---|---|---|---|---|---|
| APC | 3 | c.266C > G p.(Ser89*) | nd | NA | 5 | |
| 9 | c.147_150del p.(Lys49Asnfs*20) | nd | NA | 5 | ||
| 34 | c.1966C > G p.(Leu656Val) | rs577466163 | 0 | ARM | 3 | |
| 133 | c.7399C > A p.(Pro2467Thr) | rs372305287 | 1e-04 | APC basic | 3 | |
| 136 | c.8501A >C p.(His2834Pro) | nd | EB1_hDLG | 3 | ||
| 139 | c.1240C > G p.(Arg414Cys) | rs137854567 | nd | — | 3 | |
| AXIN2 | 55 | c.2141G > A p.(Arg714Gln) | rs762872515 | 0 | — | 3 |
| 79 | c.203G > A p.(Arg68Gln) | rs138056036 | 2e-04 | AXIN1_TNKS | 3 | |
| MUTYH | 35 | c.1187G > A p.(Gly396Asp) | rs36053993 | 4.8e-03 | NUDIX 4 | 5 |
| 35 | c.739C > G p.(Arg247Gly) | nd | ENDO3c | 4 | ||
| 37 | c.1187G > A p.(Gly396Asp) | rs36053993 | 4.8e-03 | NUDIX 4 | 5 | |
| 38 | c.1187G > A p.(Gly396Asp) | rs36053993 | 4.8e-03 | NUDIX 4 | 5 | |
| 61 | c.667A > G p.(Ile223Val) | rs200872702 | 3.4e-04 | ENDO3c | 3 | |
| 89 | c.1187G > A p.(Gly396Asp) | rs36053993 | 4.8e-03 | NUDIX 4 | 5 | |
| 89 | c.1510_1517delinsCCAACAGCCA p.Thr504Profs*68 | nd | NA | 5 | ||
| 99 | c.1187G > A p.(Gly396Asp) | rs36053993 | 4.8e-03 | NUDIX 4 | 5 | |
| NTHL1 | 16 | c.527T > C p.(Ile176Thr) | rs1805378 | 2.2e-03 | ENDO3c | 3 |
| 75 | c.856G > A p.(Gly286Ser) | rs139309757 | 3.2e-05 | ENDO3c | 3 | |
| 82 | c.527T > C p.(Ile176Thr) | rs1805378 | 2.2e-03 | ENDO3c | 3 | |
| 83 | c.268C > T p.(Gln90*) | rs150766139 | 2.0e-03 | NA | 5 | |
| POLD1 | 116 | c.2007-5C > T | rs199506387 | 2.5e-04 | NA | 1 |
| 118 | c.520C > T p.(Arg174Trp) | rs749334182 | 2.7e-05 | POLBc-exo | 3 | |
| 152 | c.2052G > C p.(Gln684His) | rs144143245 | 6.3e-04 | POLBc-pol | 3 | |
| 157 | c.1465G > A p.(Val489Met) | rs753244422 | 3.3e-05 | POLBc-exo | 3 | |
| POLE | 16 | c.3857G > A p.(Arg1286His) | rs771823596 | 5e-05 | low complex | 3 |
| 21 | c.6716C > T p.(Ala2239Val) | rs190813054 | 8e-06 | — | 2 | |
| 83 | c.141delG p.(Phe48Leufs*6) | rs761329565 | 0 | NA | 4 | |
| 147 | c.198G > A p.(Met66Ile) | rs764962999 | 0 | — | 3 |
All variants were heterozygous. †GnomAD (08/06/2018): European (Non-Finish) population frequencies (Exome + Genome). ‡PD = Protein domain from SMART protein database: NA = not applicable. §CL: variant classification: 1 = benign; 2 = likely benign; 3 = uncertain significance; 4 = likely pathogenic; 5 = pathogenic. Reference sequences: APC: NM_000038, NP_000029; AXIN2: NM_004655, NP_004646; MUTYH: NM_001128425, NP_036354; NTHL1: NM_002528, NP_002519; POLD1: NM_001256849, NP_001121897; POLE: NM_006231, NP_006222.