Table 3.
Rare missense substitutions of different DNA repair genes
| Gene | Variant | Location | Type of variant | Protein change | Pathogenic variants in other genes | Databases | ||
|---|---|---|---|---|---|---|---|---|
| dbSNP | ClinVar | gnomAD MAF | ||||||
| ATM | c.2149C > T | ex.14 | Missense | p.(Arg717Trp) |
BRCA1 c.3700_3704delGTAAA |
rs147515380 | Uncertain significance | 0.00003 |
| ATM | c.6022A > G | ex.41 | Missense | p.(Ile2008Val) | – | rs2084586855 | Uncertain significance | – |
| ATM | c.6028A > G | ex.41 | Missense | p.(Arg2010Gly) | CHEK2c.1100delC | – | Uncertain significance | – |
| BRCA2 | c.3968A > G | ex.11 | Missense | p.(Lys1323Arg) | – | – | – | – |
| BRCA2 | c.4043G > C | ex.11 | Missense | p.(Cys1348Ser) |
BRCA1 c.5266dupC |
– | – | – |
| BRCA2 | c.5624A > C | ex.11 | Missense | p.(Lys1875Thr) |
MSH6 c.1299 T > G |
rs587782583 | Uncertain significance | 0.00001 |
| MRE11 | c.1480G > A | ex.13 | Missense | p.(Glu494Lys) | – | rs104895016 | Conflicting interpretations of pathogenicity | 0.002 |
| MRE11 | c.1492G > A | ex. 13 | Missense | p.(Asp498Asn) | – | rs564511708 | Uncertain significance | 0.002 |
| MSH6 | c.926C > G | ex.4 | Missense | p.(Ser309Cys) | – | rs544222338 | Conflicting interpretations of pathogenicity | 0.002 |
| MUTYH | c.985G > A | ex.11 | Missense | p.(Val329Met) |
MSH6 c.1299 T > G |
rs147718169 | Conflicting interpretations of pathogenicity | 0.00008 |
| MUTYH | c.1187G > A | ex.13 | Missense, Splice region | p.(Gly396Asp) | – | rs36053993 | Likely pathogenic | 0.003 |
| NBN | c.515T > C | ex.5 | Missense | p.(Val172Ala) | – | – | – | – |
| NBN | c.1912T > C | ex. 12 | Missense, Splice region | p.(Ser638Pro) | – | rs199657566 | Uncertain significance | 0.00003 |
| PALB2 | c.315G > C | ex. 4 | Missense | p.(Glu105Asp) | – | rs515726108 | Uncertain significance | 0.00003 |
| PALB2 | c.1486G > C | ex.4 | Missense | p.(Asp496His) |
BRCA1 c.3143delG |
– | – | – |