Rare, non-synonymous/truncating or missense variants in WNK2 identified in additional international SPS cohorts
| Variant | Exon | gnomAD | Allele number | Number of homozygotes | CADD | Patient | SPS criteria | Onset age | CRC index case | Cohort |
| c.106_107insG (p.Pro36Argfs*121) | 1 | 0 | 0 | 0 | N/A | BN-174 | 1,3 | 22 | N | DE |
| c.1853G>A (p.Ser618Asn) | 8 | 0 | 0 | 0 | 26.4 | RB-1 | 1 | 57 | N | NL |
| c.2758G>A (p.Ala920Thr) | 11 | 0.0001315 | 20/152 056 | 0 | 15 | GCP208001 | 1,3 | 27 | N | AU |
| c.3418G>A (p.Gly1140Ser) | 14 | 0 | 0 | 0 | 23.9 | MUC-6 | 1,3 | 42 | NA | DE |
| c.3623C>T (p.Thr1208Met) | 15 | 0.000006582 | 1/151 930 | 0 | 26.6 | MUC-4 | * | 30 | N | DE |
| c.5476C>T (p.Arg1826Trp) | 23 | 0 | 0 | 0 | 25.1 | BN-210 | 3 | 55 | N | DE |
| c.5656C>T (p.Arg1886Trp) | 23 | 0.002233 | 219/152 194 | 1 | 21.2 | RB-2 | † | 51 | N | NL |
| BN-145 | 3 | 29 | NA | DE | ||||||
| MUC-1116–01 | 1 | 20 | N | DE | ||||||
| c.5906C>G (p.Pro1969Arg) | 24 | 0 | 0 | 0 | 25.3 | GCP038001 | 3 | 59 | N | AU |
| c.6080C>G (p.Ala2027Gly) | 25 | 0 | 0 | 0 | 25.1 | BN-83 | 3 | 18 | NA | DE |
| c.6512G>A (p.Ser2171Asn) | 28 | 0 | 0 | 0 | 23 | BN-104 | 1,3 | 21 | NA | DE |
A cut-off of 15 was used to selected possible pathogenic variants. SPS criteria: according to the 2010 WHO SPS clinical criteria.
*This patient did not fulfil SPS criteria but presented a large serrated polyp at 30 and strong CRC family history.
†This patient presented a serrated polyp count between 1 and 10.
AU, Australia; CADD, Combined Annotation Dependent Depletion Phred score; CRC, colorectal cancer; DE, Germany; gnomAD, Genome Aggregation Database variant frequency; N, no; NA, not available; NL, Netherlands; SPS, serrated polyposis syndrome; Y, yes.