Rare germline variants identified in the WNK2 gene in the discovery and validation SPS cohorts
| Variant | Exon | Prediction tools | gnomAD | Allele count | Number of homzygotes | Family | SPS criteria | CRC index case | CRC family history | Cohort |
| c.2105C>T (p.Pro702Leu) | 9 | 5 | 0.000125 | 19/152,210 | 0 | PanSPS_044 | 3 | Y | N | Validation |
| c.3341C>T (p.Thr1114Met) | 12 | 3 | 0.0000526 | 8/152,182 | 0 | PanSPS_078 | 1 | N | Y | Validation |
| c.4820C>T (p.Ala1607Val) | 20 | 5 | 0.000138 | 21/152,228 | 0 | CAR_SPS.4 | 1,3 | N | Y | Discovery |
| c.5588T>C (p.Leu1863Pro) | 23 | 5 | 0 | 0 | 0 | PanSPS_055 | 3 | N | N | Validation |
| c.6157G>A (p.Val2053Ile) | 25 | 5 | 0.0000657 | 10/152,200 | 0 | CAR_SPS.6 | 2,3 | N | Y | Discovery |
Prediction tools: number of pathogenicity positive predictions according to missense bioinformatics prediction tools (PhyloP, SIFT, Polyphen, MutationTaster, CADD and LRT). SPS criteria: according to the 2010 WHO SPS clinical criteria. CRC family history: defined as presence of any CRC case in the family besides the index case.
CRC, colorectal cancer; gnomAD, Genome Aggregation Database; N, no; SPS, serrated polyposis syndrome; Y, yes.