Table 2.
characteristics of the patients with variants other than SMAD6.
| Patient | Sex | Age of molecular diagnosis (months) | Affected suture | Gene | Exon | Genomic position (hg38) | MAF max (gnomADv3) | Protein | dbSNP (build 155) | MAF max/MAF total (gnomADv3) | SIFT | Polyphen HumVar | CADD | Fathmm | REVEL | Meta LR | Maxent | SpliceAI (score 0-1) | SPIP risk [0% - 100%] | HGMD-pro | ClinVar | Inheritance | ACMG parameters | ACMG classification |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 8 | F | 9 | S | FGFR2 | 2 | chr10: g.121593750 G > T | NM_000141.5: c.68 C > A | p.(Pro23His) | rs774554190 | 0.00021 (SA)/0.000007 | D | PD | 26.5 | T | D | D | - | 0 | 5% | No | No | unaffected mother | PM1, PM2, PP2, PP3, PP4 | VUS |
| 9 | M | 7 | S | FGFR2 | 8 | chr10: g.121520098 C > T | NM_000141.5: c.820 G > A | p.(Val274Ile) | rs1488169619 | 0.000024 (AF)/0.000013 | D | PD | 23.4 | D | D | D | - | 0 | 7.8% | No | No | unaffected father | PM1, PM2, PP2, PP3, PP4 | VUS |
| 10 | M | 10 | M | FREM1 | 1 to 9 | NM_144966.5: c. (? _ 1); (1393 + 1_1394-1) del | p.? | - | - | - | - | - | No | No | unaffected father | |||||||||
| 11 | M | 6 | S | TWIST1 | 1 | chr7: g.19117152 C > G | NM_000474.4: c.170 G > C | p.(Gly57Ala) | no | not described | T | B | 8.5 | D | U | B | AL: 3.69 > −4.58 = −224% | 0 | 2.5% | No | No | unaffected father | PM2, PM4 | VUS |
| 12 | M | 8 | S | ALX4 | 2 | chr11: g.44275479 G > A | NM_021926.4: c.646 C > T | p.(Arg216Trp) | rs587777700 | 0.000024 (AF)/0.000007 | D | PD | 25.6 | D | D | D | - | 0 | 3.5% | Yes | 000155902.1 | unaffected mother | PM1, PM2, PP2, PP4, PM5 | LP |
| 13 | F | 8 | S | TCF12 | 11 | chr15: g.57234035 A > G | NM_207036.2: c.971-8 A > G | p.? | no | not described | - | - | 23.4 | - | - | - | AL: −109% AG: 198% | AL:0.51 and AG:0.95 | 98.4% | No | No | unaffected father | PM2, PP3, PP4 | VUS |
All frequencies from GnomAD and HGMD-pro. SPIP: the risk for the variant to alter splicing [79.27–91.06%].
P possibly damaging, B benign, U uncertain, AG acceptor gain, AL acceptor loss, SA South Asian, AF African/African American, LP likely pathogenic, P pathogenic, T tolerated, S sagittal, M metopic.