Table 2.
Genetic variants of the included patients: all patients were heterozygous unless stated otherwise. Patient ID17 is listed twice due to two variants detected but only counted once. ERA, established risk allele; LRP5*, individual 17 (ID 17) carries two variants in the LRP5 gene; LRP5§, homozygous, all other heterozygous; N, no treatment; A, antiresorptive treatment; R, romosozumab treatment; AA, amino acid
| ID | Affected gene | Treatment | Base | AA Change | ACMG class | ACMG criteria | gnomAD frequency (total) | ||
|---|---|---|---|---|---|---|---|---|---|
| N | A | R | |||||||
| 1 | LRP5 | X | c.2377G>A | p.(Gly793Arg) | 4 | PM2_sup, PP3_str, PP4 | Absent | ||
| 2 | WNT1 | X | c.754G>C | p.(Gly252Arg) | 3 | PM2_sup, PP3_mod | 5.1 × 10−4 | ||
| 3 | LRP5 | X | c.2377G>A | p.(Gly793Arg) | 3 | PM2_sup, PP3_str, PP4 | Absent | ||
| 4 | LRP6 | X | X | c.775C>T | p.(Arg259Cys) | 3 | PM2_sup, PP3 | 8.8 × 10−5 | |
| 5 | WNT1 | X | c.703C>T | p.(Arg235Trp) | 5 | PS3, PS4, PM2_sup, PP1, PP3 | Absent | ||
| 6 | WNT1 | X | c.703C>T | p.(Arg235Trp) | 5 | PS3, PS4, PM2_sup, PP1, PP3 | Absent | ||
| 7 | WNT1 | X | X | c.264T>A | p.(Ser88Arg) | ERA | Association Study_str | 0.003 | |
| 8 | LRP5 | X | c.3107G>A | p.(Arg1036Gln) | ERA | Association Study_vstr, Functional Study | 0.004 | ||
| 9 | LRP5 | X | X | c.2829G>A | p.(Pro943 =) | 2–3 | PM2_sup, BP4 | 4.4 × 10−4 | |
| 10 | LRP5 | X | c.1141G>A | p.(Asp381Asn) | 4 | PS4, PM2_sup, PP3_mod, PP4 | 4 × 10−6 | ||
| 11 | LRP5 | X | c.3403C>T | p.(Arg1135Cys) | 4 | PS4, PM2_sup, PP3, PP4 | 2.6 × 10−4 | ||
| 12 | LRP5 | X | c.3403C>T | p.(Arg1135Cys) | 4 | PS4, PM2_sup, PP3, PP4 | 2.6 × 10−4 | ||
| 13 | LRP5 | X | c.1067C>T | p.(Ser356Leu) | 5 | PS1, PS3, PM2_sup, PP3_mod | 6.7 × 10−5 | ||
| 14 | LRP5 | X | c.1999G>A | p.(Val667Met) | ERA | Association Study_vstr, Functional Study | 0.038 | ||
| 15 | LRP5 | X | c.2134G>A | p.(Val712Met) | 3 | PM2_sup, PP3 | 2.4 × 10-5 | ||
| 16 | LRP5 | X | X | c.1999G>A | p.(Val667Met) | ERA | Association Study_vstr, Functional Study | 0.038 | |
| 17 | LRP5* | X | c.1999G> A | p.(Val667Met) | ERA | Association Study_vstr, Functional Study | 0.038 | ||
| 17 | LRP5* | X | c.2989C>T | p.(Ala1330Val) | ERA | Association Study_vstr | 0.13 | ||
| 18 | LRP5 | X | c.2234C>A | p.(Ala745Val) | 4 | PS4, PM2_sup, PP3_mod, PP4 | Absent | ||
| 19 | LRP5 | X | c.2234C>A | p.(Ala745Val) | 4 | PS4, PM2_sup, PP3_mod, PP4 | Absent | ||
| 20 | LRP5 | X | X | c.1999C>A | p.(Val667Met) | ERA | Association Study_vstr, Functional Study | 0.038 | |
| 21 | LRP5§ | X | c.1999C>A | p.(Val667Met) | ERA | Association Study_vstr, Functional Study | 0.038 | ||
| 22 | LRP6 | X | c.1396G>A | p.(Gly466Arg) | 3 | PM2_sup, PP3_str | Absent | ||
| 23 | WNT1 | X | c.481delG | p.(Gly162Alafs*37) | 4 | PVS1_str, PM2_sup, PP4 | Absent | ||
| 24 | LRP5 | X | c.1999G>A | p.(Val667Met) | ERA | Association Study_vstr, Functional Study | 0.038 | ||
| 25 | LRP5 | X | X | c.1999G> A | p.(Val667Met) | ERA | Association Study_vstr, Functional Study | 0.038 | |
| 26 | LRP5 | X | c.3403C>T | p.(Arg1135Cys) | 4 | PS4, PM2_sup, PP3, PP4 | 2.6 × 10−4 | ||
| 27 | LRP5 | X | c.3245A>G | p.(Tyr1082Cys) | 4 | PS4_mod, PM2_sup, PP3_str | 9.9 × 10−5 | ||