TABLE 3.
Thirty‐three Variants of unknown significance (VUS) identified in 40 young Rwandan patients.
| Gene | Reference sequence | Variant | Protein effect | Coding impact | rsID | No. carriers | GMAF | MAF—Africa |
|---|---|---|---|---|---|---|---|---|
| ATM | NM_000051.4 | c.4339A>C | p.(Ser1447Arg) | missense | NA | 1 | NA | NA |
| ATM | NM_000051.4 | c.2289 T > A | p.(Phe763Leu) | missense | rs34231402 | 1 | 0.0005 | 0.002 |
| ATM | NM_000051.4 | c.131A>Ga | p.(Asp44Gly) | missense | rs150143957 | 1 | 0.00003 | 0.0005 |
| BARD1 | NM_000465.4 | c.1148 T > A | p.(Met383Lys) | missense | rs763596413 | 1 | 0.000008 | 0 |
| BARD1 | NM_000465.4 | c.421C>T | p.(Pro281Leu) | missense | NA | 1 | NA | NA |
| BLM | NM_001287248.2 | c.3879A>G | p.(Glu1293=) | synonymous | rs28377085 | 1 | 0.00031 | 0.00314 |
| BLM | NM_001287248.2 | c.1881 T > C | p.Thr627 | synonymous | rs148678729 | 1 | 0.00003 | 0.0002 |
| BRCA1 | NM_007294.4 | c.5411 T > C | p.(Met1804 Thr) | missense | rs55808233 | 1 | 0.0002 | 0.0018 |
| BRCA1 | NM_007294.4 | c.−16A>G | 5'UTR Substitution | rs777262055 | 1 | 1.00E−05 | 3.00E−05 | |
| BRCA2 | NM_000059.4 | c.7502A>G | p.(Gln2501Arg) | missense | NA | 1 | NA | NA |
| BRIP1 | NM_032043.3 | c.778A>G | p.(Thr260Ala) | missense | rs138743097 | 1 | 0.0004 | 0.002 |
| BRIP1 | NM_032043.3 | c.854A>Ga | p.(His285Arg) | missense | rs141055990 | 1 | 0.0004 | 0.0002 |
| CDH1 | NM_004360.5 | c.1004G>Aa | p.(Arg335Gln) | missense | rs373364873 | 1 | 0.00003 | NA |
| CHEK2 | NM_001005735.2 | c.1298A>Ga | p.(Tyr433Cys) | missense | rs200928781 | 11 | 0.0000 | NA |
| CHEK2 | NM_001005735.2 | c.1270A>Ga | p.(Met424Val) | missense | rs375130261 | 3 | 0.00003 | NA |
| EPCAM (3’UTR) | NM_002354.3 | c.78A>T | 3'UTR substitution | rs568965134 | 1 | 0.0002 | 0.001 | |
| MLH1 | NM_000249.4 | c.380+16C>G | intronic | rs121909452 | 1 | NA | NA | |
| MLH1 | NM_000249.4 | c.1730C>Ta | p.(Ser577Leu) | missense | rs56185292 | 1 | 0.00006 | 0 |
| MRE11A | NM_005591.4 | c.256G>Aa | p.(Asp86Asn) | missense | rs763902512 | 1 | 0.00001 | 0.00002 |
| MRE11A | NM_005591.4 | c.2080‐23A>G | intronic substitution | rs142331797 | 1 | 0.0008 | 0.0002 | |
| MSH2 | NM_000251.3 | c•1C>G | 3'UTR substitution | rs114545543 | 1 | 0.0004 | 0.0009 | |
| MSH2 | NM_000251.3 | c.301G>C | p.(Glu101Gln) | missense | NA | 1 | NA | NA |
| MUTYH | NM_001128425.2 | c.217G>A | p.(Glu73Lys) | missense | rs1064794128 | 1 | NA | NA |
| NBN | NM_001024688.3 | c.1711A>G | p.(Lys571Glu) | missense | rs587780090 | 1 | 0.00001 | 0 |
| NBN | NM_001024688.3 | c.1354A>C | p.(Thr452Pro) | missense | rs141137543 | 1 | 0.0004 | 0.0009 |
| PMS2 | NM_000535.7 | c.924G>C | p.(Glu308Asp) | missense | rs114185660 | 1 | 0.0004 | 0.001 |
| PMS2 | NM_000535.7 | c.1004A>Ga | p.(Asn335Ser) | missense | rs200513014 | 1 | 0.00004 | 0 |
| PMS2 | NM_000535.7 | c.2350G>A | p.(Asp784Asn) | missense | rs143340522 | 3 | 0.0013 | 0.00695 |
| PMS2 | NM_000535.7 | c.130_131delinsCT | p.(Leu458Ser) | missense | rs587778615 | 10 | NA | NA |
| RAD51C | NM_058216.3 | c.965+28C>T | intronic substitution | NA | 1 | NA | NA | |
| RAD51D | NM_001142571.2 | c.322C>T | p.(Arg108Cys) | missense | rs142387263 | 1 | 0.0004 | 0.001 |
| TP53 | NM_000546.6 | c.993+165_993+166dup | intronic insertion | rs775788764 | 1 | 0 | 0 | |
| XRCC2 | NM_005431.2 | c.*3 T > C | 3'UTR Substitution | rs754786665 | 1 | 8.89E−06 | 0 |
Note In bold: Very rare variants (with GMAF ≈ 0); In italic: Novel variants;a Variants predicted by SIFT, Provean, Polyphen‐2 and MutationTaster to be damaging on the protein.