From: Expanding ACMG variant classification guidelines into a general framework
Gene | Varianta | Number of HCP families (family description) reportedb | Reference(s) | Biological/functional consequence | gpAF (hspAF) in gnomADc |
---|---|---|---|---|---|
PRSS1 | Trypsinogen gene triplication | 5 (10 patients across 4 generationsd) | Le Maréchal et al. [27] | GoF (gene dosage) [39] | Absent |
Double “gain-of-function” hybrid variant | 1 (6 patients across 3 generations) | Masson et al. [75] | GoF (gene dosage plus effect of p.Asn29Ile) | Absent | |
c.47C > T (p.Ala16Val) | 2 (4 patients across 2 generations; 3 patients across 2 generations) | Grocock et al. [76] | GoF (increased activation) [77] | Absent [78] | |
c.62A > C (p.Asp21Ala) | 1 (5 patients across 3 generations) | Yilmaz et al. [79] | GoF (increased activation) [80] | Absent | |
c.63_71dup (p.Lys23_Ile24insIleAspLys | 1 (3 patients across 2 generations) | Joergensen et al. [81] | GoF (increased activation) [81] | Absent | |
c.86A > T (p.Asn29Ile) | The second most frequent variant causing HCP [38]; in the first report, one family had 19 patients across 7 generations [82] | Gorry et al. [82] | GoF (increased activation and stability) [77] | Absent | |
c.86A > C (p.Asn29Thr) | 1 (8 patients across 3 generations) | Dytz et al. [83] | GoF (increased activation and stability) [77] | Absent | |
c.116T > C (p.Val39Ala) | 1 (9 patients across 3 generations) | Arduino et al. [84] | GoF (increased stability) [77] | Absent | |
c.311T > C (p.Leu104Pro) | 2 (both having 3 patients across 3 generations) | GoP (intracellular retention and elevation of ER stress marker) [87] | Absent | ||
c.346C > T (p.Arg116Cys) | 2 (3 patients across 2 generations; 3 patients across 3 generations) | GoP (intracellular retention and elevation of ER stress marker) [89] | 0.00007072 (0.0007018, East Asian) | ||
c.365G > A (p.Arg122His) | The most frequent variant causing HCP [38]; in the discovery report, one family had 20 patients across 4 generations [23] | 0.00001194 (0.00002639, non-Finnish European) | |||
c.365_366GC > AT (p.Arg122His) | 1 (4 patients across 4 generations) | Howes et al. [92] | Same as above | Absent | |
CFTR | Not identified | ||||
SPINK1 | c.27DelC (p.Ser10ValfsTer5) | 1 (3 patients across 2 generations) | Le Maréchal et al. [93] | LoF (predicted complete functional loss) | 0.00001197 (0.00002896, Latino/Admixed American) |
c.41T > G (p.Leu14Arg) | 2 (both having 3 patients across 3 generations) | Király et al. [94] | LoF (experimentally demonstrated to abolish SPINK1 secretion) [94] | Absent | |
Deletion of the entire gene | 1 (3 patients across 2 generations) | Masson et al. [95] | LoF (predicted complete functional loss) | Absent | |
CTRC | Not identified |