Table 1.
Identified genes and variants per patient after specific filtering.
| Patient | Gene | Locus | Type | HGVSc,HGVSp | dbSNP ID | Mutation source | MAF Value | ACMG classification | ||
|---|---|---|---|---|---|---|---|---|---|---|
| GnomAD | 1000Genomes (China) | ExAC (East Asian) | ||||||||
| 1 | MAMLD1 | Xq28 | miss | c.1986C>G, p.S662R | mother | VUS[(PM2,BP1)] | ||||
| 1 | RET | 10q11.2 | syn | c.3120G>C, p.L1040L | mother | VUS(PM2,BP7) | ||||
| 1 | CDH23 | 10q22.1 | c.6712+37C>T | rs750966744 | father | 0.000032 | 0.0003 | VUS(PM2) | ||
| 1 | MYO7A | 11q13.5 | c.3504-39T>C | rs192929996 | mother | 0.0013 | 0.019 | 0.017 | VUS(BS1) | |
| 1 | MAML1 | 5q35 | syn | c.1893G>A, p.Q631Q | Denove | VUS(PM2,BP7) | ||||
| 2 | MAMLD1 | Xq28 | non | c.1066C>T, p.R356X | rs782347827 | mother | 0 | P(PVS1,PM2,PP3) | ||
| 2 | WNT9B | 17q21 | c.*158C>T | rs1233082195 | father | 0.000008 | VUS(PM2,PP5) | |||
| 2 | NOTCH2 | 1p13-p11 | c.2600-24C>A | rs149097658 | mother | 0.0034 | 0.024 | 0.027 | VUS(BS) | |
| 2 | GLI2 | 2q14 | c.845+10G>A | rs199673018 | father | 0.00024 | 0 | 0.0005 | VUS | |
| 2 | GLI3 | 7p13 | c.1028+15G>A | rs116842918 | father | 0.0014 | 0.012 | 0.017 | LB(BS1,BP6) | |
| 3 | MAMLD1 | Xq28 | non | c.1066C>T, p.R356X | rs782347827 | mother | 0 | P(PVS1,PM2,PP3) | ||
| 3 | MYO7A | 11q13.5 | c.1554+22C>T | mother | 0.0006 | 0.0024 | VUS(PM2,BP4) | |||
| 3 | MYO7A | 11q13.5 | miss | c.3124T>G, p.W1042G | mother | VUS(PM1,PM2,PP3) | ||||
| 4 | MAMLD1 | Xq28 | miss | c.1261G>C, p.A421P | mother | VUS(PM2,PP3,BP1) | ||||
| 4 | MAML3 | 4q28 | miss | c.1612A>G, p.M538V | rs148778901 | mother | 0.0074 | 0.0072 | 0.0078 | LB (PP3,BS1) |
| 4 | GLI3 | 7p13 | miss | c.1843A>T, p.T615S | rs200913720 | mother | 0.0006 | 0.0024 | 0.0005 | VUS (PP3,BP6) |
| 4 | GLI3 | 7p13 | miss | c.674C>T, p.T225I | rs753769482 | mother | 0.001 | VUS (PM2,PP3) | ||
| 5 | MAMLD1 | Xq28 | non | c.454C>T, p.Q152X | mother | P(PVS1,PM2,PP3) | ||||
| 5 | RET | 10q11.2 | miss | c.1465G>A, p.D489N | rs9282834 | mother | 0.0296 | 0.014 | 0.028 | LB (BS1,BP6,BP4) |
| 5 | NOTCH2 | 1p13-p11 | c.2600-24C>A | rs149097658 | father | 0.0191 | 0.024 | 0.027 | VUS (BS1) | |
| 5 | GLI2 | 2q14 | syn | c.4611C>T, p.L1537L | rs1335405295 | father | VUS (PM2,BP7) | |||
| 6 | MAMLD1 | Xq28 | miss | c.1624C>T, p.P542S | rs146443503 | mother | 0.0015 | 0.016 | 0.021 | LB (BS1,BP1) |
| 6 | MYO7A | 11q13.5 | c.6051+9C>T | rs747742075 | father | 0.0018 | VUS (BS4) | |||
| 6 | CYP1A1 | 15q24.1 | miss | c.518C>G, p.T173R | rs28399427 | father | 0.008 | 0.0072 | 0.0094 | VUS (BP4) |
| 6 | WNT9A | 1q42 | c.353-30G>A | rs141239747 | mother | 0.0314 | 0.039 | 0.028 | B (BA1,BS1,BS2) | |
| 6 | FRAS1 | 4q21.21 | syn | c.10930C>T, p.L3644L | rs183729151 | father | 0.0025 | 0.0048 | 0.0022 | LB (BS4,BP7) |
| 6 | GLI3 | 7p13 | syn | c.3015C>T, p.A1005A | rs200965852 | father | 0.0173 | 0.024 | 0.019 | LB (BS1,BP6,BP7) |
| 7 | MAMLD1 | Xq28 | miss | c.1000C>T, p. P334S | rs41313406 | mother | 0.08 | 0.0031 | 0.0002 | LP(PM1,PM2,PM5,PP3) |
| 7 | CYP1A1 | 15q24.1 | syn | c.927C>T, p.N309N | rs368742906 | unknown | 0.0031 | 0.0024 | 0.0032 | VUS (PM2,BP7,BP4) |
| 7 | PIK3R3 | 1p34.1 | miss | c.290A>G, p.Q97R | rs1225342856 | unknown | VUS (PM1,PM2) | |||
| 8 | MAMLD1 | Xq28 | non | c.370C>T, p.Q124X | mother | P(PVS1,PM2) | ||||
| 8 | CDH23 | 10q22.1 | miss | c.1282G>A, p.D428N | rs188376296 | father | 0.0031 | 0.0048 | 0.0066 | VUS (PP5,PP3,BS4) |
| 8 | MYO7A | 11q13.5 | miss | c.1133G>A, p.R378H | rs397516282 | father | LP (PM2,PM5,PP3,BS4) | |||
| 8 | MYO7A | 11q13.5 | c.4152+15A>G | rs1033447071 | father | VUS (PM2,BS4) | ||||
| 8 | FREM2 | 13q13.3 | miss | c.4916G>A, p.R1639K | rs77886481 | mother | 0.0197 | 0.014 | 0.022 | VUS (BS1) |
| 8 | FRAS1 | 4q21.21 | c.7372-24A>G | rs78365404 | mother | 0.013 | 0.0096 | 0.019 | B (BS1,BS2,BS4) | |
| 8 | FRAS1 | 4q21.21 | miss | c.8493C>G, p.F2831L | rs774409872 | mother | 0.0019 | – | – | VUS (BS4) |
| 9 | MAMLD1 | Xq28 | miss | c.2975C>T, p.T992I | mother | VUS(PM2,BP1,BP4) | ||||
| 9 | CDH23 | 10q22.1 | c.9077+7C>T | rs76114420 | mother | 0.0259 | 0.022 | 0.018 | LB (BS1,BP6) | |
| 9 | WNT9B | 17q21 | syn | c.1059C>T, p.Y353Y | rs537242221 | mother | 0.0006 | 0.0024 | 0 | VUS (BP7) |
| 9 | MAML3 | 4q28 | miss | c.2969C>T, p.P990L | rs185593153 | father | 0.0006 | 0.0048 | 0.0011 | VUS |
| 9 | FRAS1 | 4q21.21 | c.5857-434C>T | mother | VUS (PM2,BS4) | |||||
| 10 | MAMLD1 | Xq28 | miss | c.2780C>T, p.R927L | rs782511956 | mother | LB (PM2,BP1,BP4) | |||
| 10 | CDH23 | 10q22.1 | c.4210-16C>A | rs775928557 | father | VUS (PM2) | ||||
| 10 | CDH23 | 10q22.1 | c.9077+7C>T | rs76114420 | mother | 0.0259 | 0.022 | 0.018 | LB (BS1,BP6) | |
| 10 | MYO7A | 11q13.5 | syn | c.324C>T, p.Y108Y | rs116892396 | mother | 0.0161 | 0.026 | 0.021 | LB (BS1,BP6,BP7) |
| 10 | MAML2 | 11q21 | miss | c.385G>A, p.D129N | rs892433964 | mother | 0.0012 | VUS (PP3) | ||
| 10 | PTPN11 | 12q24 | c.1448-38G>T | mother | VUS (PM2) | |||||
| 10 | NOTCH2 | 1p13-p11 | syn | c.6783G>A, p.E2261E | rs759118563 | mother | 0.0001 | VUS (PM2,BP7) | ||
| 10 | PIK3R3 | 1p34.1 | miss | c.950A>G, p.N317S | rs114180250 | father | 0.0129 | 0.019 | 0.013 | VUS (BS1) |
| 10 | EVC | 4p16 | c.1316-20G>T | rs773461223 | mother | VUS (PM2) | ||||
| 10 | EVC | 4p16 | c.1564-6C>T | rs188245524 | mother | 0.0012 | 0.0024 | 0.0038 | VUS (BP6,BP4) | |
| 10 | FRAS1 | 4q21.21 | miss | c.6569C>T, p.S2190F | rs200166354 | father | 0.0031 | 0.0024 | 0.0033 | VUS (BS4) |
| 10 | FLNA | Xq28 | syn | c.3756G>A, p.A1252A | rs186619828 | mother | 0 | 0 | 0 | VUS (BP6) |
ACMG, the American College of Medical Genetics and Genomics; MAF, Minor Allele Frequency; VUS, Uncertain Significance; P, Pathogenic; B, Benign; LB, Likely Benign; LP, Likely Pathogenic.