Table 2.
Sample ID | Gene Name | HGVS.c | HGVS.p | Variant Impact | gnomAD | ClinVar | COSMIC | PolyPhen2 | SIFT | CADD | Tumor AF | Average Sample AF | LOH AF Increase over Average (%) | LOH |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Biallelic Somatic Variants | ||||||||||||||
LLS02 | MSH3 | c.423C > A | p.Cys141 * | stop_gained | not present | not present | not present | - | - | 38 | 0.60 | 0.35 | 73 | yes |
LLS09 | MSH3 | c.1148delA | p.Lys383fs | frameshift_variant | 1.64399 × 10−5 | Pathogenic | COSM1438888 | - | - | - | 0.46 | 0.33 | 40 | yes |
LLS10 | MSH3 | c.1148delA | p.Lys383fs | frameshift_variant | 1.64399 × 10−5 | Pathogenic | COSM1438888 | - | - | - | 0.61 | 0.35 | 75 | yes |
LLS10 | POLD1 | c.583C > T | p.Arg195 * | stop_gained | 0.000647 | Conflicting | not present | - | - | 37 | 0.36 | 0.35 | 5 | no |
LLS10 | POLD1 | c.2959delG | p.Asp987fs | frameshift_variant | 0.000057209 | not present | COSM3686158 | - | - | - | 0.40 | 0.35 | 15 | no |
LLS17 | MLH1 | c.129dupA | p.Ser44fs | frameshift_variant | not present | Pathogenic | not present | - | - | - | 0.22 | 0.25 | −14 | no |
LLS17 | MLH1 | c.1831delA | p.Ile611fs | frameshift_variant | not present | not present | not present | - | - | - | 0.33 | 0.25 | 31 | no |
LLS18 | MSH2 | c.2251G > T | p.Gly751 * | stop_gained | not present | not present | not present | - | - | 48 | 0.15 | 0.17 | −11 | no |
LLS18 | MSH2 | c.2634+1G > A | - | splice_variant | not present | Likely_pathogenic | not present | - | - | 27.6 | 0.19 | 0.17 | 14 | no |
LLS21 | MLH1 | c.199G > A | p.Gly67Arg | missense_variant | not present | Pathogenic | COSM1422567 | D | D | 34 | 0.13 | 0.18 | −25 | no |
LLS21 | MLH1 | c.602delT | p.Val201fs | frameshift_variant | not present | not present | not present | - | - | - | 0.24 | 0.18 | 36 | no |
LLS5159 | POLD1 | c.1562G > A | p.Arg521Gln | missense_variant | 0.000126296 | VUS | not present | P | D | 31 | 0.22 | 022 | 4 | no |
LLS5159 | POLD1 | c.3047G > A | p.Arg1016His | missense_variant | not present | VUS | COSM7587416 | P | D | 29.6 | 0.27 | 0.22 | 25 | no |
LLS9045 | MLH3 | c.3694C > T | p.Arg1232Cys | missense_variant | 3.24934 × 10−5 | VUS | not present | D | D | 31 | 0.28 | 0.28 | 4 | no |
LLS9045 | MLH3 | c.1924T > C | p.Phe642Leu | missense_variant | not present | not present | not present | B | D | 20.1 | 0.46 | 0.28 | 68 | yes |
LLS9045 | MLH1 | c.588delA | p.Lys196fs | frameshift_variant | 4.06276 × 10−6 | Pathogenic | not present | - | - | - | 0.22 | 0.28 | −21 | no |
LLS9045 | MLH1 | c.1489delC | p.Arg497fs | frameshift_variant | 4.06078 × 10−6 | not present | COSM1422596 | - | - | - | 0.21 | 0.28 | −23 | no |
LLS9049 | POLD1 | c.2959delG | p.Asp987fs | frameshift_variant | 0.000057209 | not present | COSM3686158 | - | - | - | 0.31 | 0.19 | 57 | yes |
Monoallelic Somatic Variants | ||||||||||||||
LLS09 | MSH6 | c.3552G > A | p.Met1184Ile | missense_variant | 4.06835 × 10−6 | not present | not present | B | T | 28 | 0.30 | 0.33 | −10 | no |
LLS10 | MSH6 | c.2875C > T | p.Arg959Cys | missense_variant | 1.22491 × 10−5 | VUS | not present | P | D | 27.2 | 0.34 | 0.35 | −1 | no |
LLS10 | POLE | c.2091delC | p.Leu698fs | frameshift_variant | 8.20836 × 10−6 | VUS | COSM4612998 | - | - | - | 0.27 | 0.35 | −21 | no |
LLS18 | MSH6 | c.3261dupC | p.Phe1088fs | frameshift_variant | 0.00003449 | Pathogenic | COSM13394 | - | - | - | 0.13 | 0.17 | −23 | no |
LLS19 | MSH2 | c.1225C > T | p.Gln409 * | stop_gained | not present | Pathogenic | COSM7508782 | - | - | 41 | 0.16 | 0.15 | 7 | no |
LLS19 | MSH6 | c.1993G > A | p.Glu665Lys | missense_variant | 4.06792 × 10−6 | not present | not present | P | T | 24.9 | 0.12 | 0.15 | −18 | no |
LLS21 | MSH3 | c.3356T > C | p.Leu1119Pro | missense_variant | not present | not present | not prensent | D | D | 27.3 | 0.14 | 0.18 | −20 | no |
LLS21 | PMS2 | c.1239delA | p.Asp414fs | frameshift_variant | not present | not present | COSM150905 | - | - | - | 0.20 | 0.18 | 12 | no |
LLS21 | POLE | c.1060A > G | p.Thr354Ala | missense_variant | not present | not present | not present | B | T | 22.5 | 0.20 | 0.18 | 11 | no |
LLS9045 | MUTYH | c.724C > T | p.Arg242Cys | missense_variant | 5.29614 × 10−5 | Pathogenic | COSM6954579 | D | D | 29.5 | 0.36 | 0.28 | 32 | no |
LLS9045 | POLD1 | c.735G > T | p.Glu245Asp | missense_variant | not present | not present | not present | D | T | 22.9 | 0.27 | 0.28 | −2 | no |
LLS9049 | MUTYH | c.544C > T | p.Arg182Trp | missense_variant | 1.21817 × 10−5 | not present | COSM6922477 | D | T | 23.3 | 0.13 | 0.19 | −32 | no |
LLS9049 | MSH3 | c.433G > T | p.Ala145Ser | missense_variant | not present | VUS | not present | P | T | 17.64 | 0.15 | 0.19 | −23 | no |
LLS9049 | POLE | c.3176G > A | p.Arg1059His | missense_variant | 1.21838 × 10−5 | not present | COSM6965827 | D | D | 35 | 0.20 | 0.19 | 2 | no |
Rows in bold are showing when LOH is associated. GnomAD: allele frequency from gnomAD database. PolyPhen2: B: benign; P: probably pathogenic; D: deleterious; SIFT: T: tolerable; D: deleterious. Tumor AF: alternative allele frequency. Average AF: average of all exome variants over 0.1 of AF. LOH loss of heterozygosity. CADD: Phred score version 1.6. VUS: variant of uncertain significance. HGVS.c: coding variant. HGVS.p: protein level variant. * stop gained codon.