Table 2 List of the genetic variants identified in DPYD by next generation sequencing.
Position (GRCh37) | Ref | Alt | Statut | Number of patients | Allele Freq. | HGVS | dbSNP ID | Allele | Transcript consequences | SIFT (score) | PolyPhen (score) | CADD(score) | ClinVar ID | GnomAD (Eur. MAF) | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Total | Deficient | Coding DNA | Protein | |||||||||||||
MAF ≥ 1% | ||||||||||||||||
chr1:97770920 | C | T | Het | 293 | 81 (28%) | 5.10% | c.2194G>A | p.Val732Ile | rs1801160 | *6 | missense variant | T (0.1) | B (0.30) | 24.4 | 100080 | 4.53% |
Hom | 5 | 1 (20%) | ||||||||||||||
chr1:97915624 | A | G | Het | 208 | 32 (15%) | 3.63% | c.1896T>C | p.Phe632Phe | rs17376848 | synonymous variant | 3.576 | 100088 | 5.04% | |||
Hom | 4 | 0 (0%) | ||||||||||||||
chr1:97981395 | T | C | Het | 951 | 178 (19%) | 20.24% | c.1627A>G | p.Ile543Val | rs1801159 | *5 | missense variant | D (0.04) | B (0) | 15.46 | 100092 | 19.52% |
Hom | 126 | 15 (12%) | ||||||||||||||
chr1:97981421 | C | T | Het | 136 | 31 (23%) | 2.36% | c.1601G>A | p.Ser534Asn | rs1801158 | *4 | missense variant | D (0.01) | B (0.03) | 22.8 | 100094 | 1.43% |
Hom | 2 | 2 (100%) | ||||||||||||||
chr1:98039419 | C | T | Het | 97 | 19 (20%) | 1.67% | c.1236G>A | p.Glu412Glu | rs56038477 | hapB3 | synonymous variant | 9.659 | 100100 | 1.40% | ||
Hom | 1 | 0 (0%) | ||||||||||||||
chr1:98165091 | T | C | Het | 486 | 113 (23%) | 8.92% | c.496A>G | p.Met166Val | rs2297595 | missense variant | D (0) | PD (0.99) | 24.8 | 100116 | 8.59% | |
Hom | 22 | 2 (9%) | ||||||||||||||
chr1:98348885 | A | G | Het | 930 | 180 (19%) | 22.98% | c.85T>C | p.Cys29Arg | rs1801265 | *9A | missense variant | T (1) | B (0) | 435 | 22.45% | |
Hom | 218 | 40 (18%) | ||||||||||||||
1% > MAF ≥ 0. 1% | ||||||||||||||||
chr1:97544543 | G | T | Het | 5 | 3 (60%) | 0.08% | c.3067C>A | p.Pro1023Thr | rs114096998 | missense variant | D (0) | B (0.42) | 18.94 | 100069 | 0.36% | |
chr1:97547947 | T | A | Het | 22 | 15 (68%) | 0.37% | c.2846A>T | p.Asp949Val | rs67376798 | missense variant | D (0) | PD (0.52) | 25.3 | 88974 | 0.29% | |
chr1:97915614 | C | T | Het | 12 | 8 (67%) | 0.20% | c.1905+1G>A | p.(?) | rs3918290 | *2A | splice donor variant | 33 | 432 | 0.57% | ||
chr1:97981343 | A | C | Het | 11 | 6 (55%) | 0.19% | c.1679T>G | p.Ile560Ser | rs55886062 | *13 | missense variant | D (0) | PD (0.94) | 27.9 | 88975 | 0.031% |
chr1:98015269 | G | A | Het | 7 | 0 (0%) | 0.12% | c.1371C>T | p.Asn457Asn | rs57918000 | synonymous variant | 11.57 | 100097 | 0.24% | |||
chr1:98039437 | C | T | Het | 5 | 2 (40%) | 0.08% | c.1218G>A | p.Met406Ile | rs61622928 | missense variant | T (0.31) | B (0) | 19.85 | 100101 | 0.67% | |
chr1:98144726 | T | C | Het | 8 | 2 (25%) | 0.13% | c.775A>G | p.Lys259Glu | rs45589337 | missense variant | D (0) | PD (0.62) | 23 | 235464 | 0.61% | |
MAF ≤ 0.1% | ||||||||||||||||
chr1:97544541 | C | T | Het | 1 | 0 | 0.02% | c.3069G>A | p.Pro1023Pro | rs749122978 | synonymous variant | D (0) | B (0.42) | 0.179 | NA | 0.002% | |
chr1:97547907 | G | A | Het | 1 | 0 | 0.02% | c.2886C>T | p.Thr962Thr | rs368617815 | synonymous variant | 11.25 | NA | 0.006% | |||
chr1:97547921 | T | C | Het | 3 | 3 (100%) | 0.05% | c.2872A>G | p.Lys958Glu | rs141044036 | missense variant | D (0.01) | PD (1) | 28.9 | 551659 | 0.002% | |
chr1:97564044 | C | T | Het | 1 | 0 | 0.02% | c.2766+1G>A | p.(?) | rs1355754530 | splice donor variant | 34 | NA | 0.001% | |||
chr1:97564177 | A | C | Het | 1 | 0 | 0.02% | c.2634T>G | p.Ser878Arg | rs919596571 | missense variant | T (0.36) | B (0.00) | 23 | 874134 | 0.001% | |
chr1:97658667 | CT | C | Het | 1 | 0 | 0.02% | c.2579del | p.Gln860Argfs*9 | rs746991079 | frameshift variant | 34 | 551707 | 0.004% | |||
chr1:97658736 | C | A | Het | 1 | 0 | 0.02% | c.2511G>T | p.Leu837Leu | rs763174477 | synonymous variant | 9.956 | NA | 0.016% | |||
chr1:97700416 | C | T | Het | 1 | 0 | 0.02% | c.2434G>A | p.Val812Ile | rs371313778 | missense variant | T (0.11) | B (0.03) | 22.9 | NA | 0.012% | |
chr1:97700495 | C | T | Het | 1 | 0 | 0.02% | c.2355G>A | p.Leu785Leu | NA | synonymous variant | 10.03 | NA | ||||
chr1:97700520 | G | T | Het | 1 | 1 | 0.02% | c.2330C>A | p.Ala777Asp | rs374825099 | missense variant | T (0.05) | B (0.4) | 25.5 | NA | 0.003% | |
chr1:97700547 | G | T | Het | 1 | 0 | 0.02% | c.2303C>A | p.Thr768Lys | rs56005131 | missense variant | T (0.16) | B (0.05) | 22.7 | 287480 | 0.019% | |
chr1:97771751 | C | T | Het | 3 | 1 (33%) | 0.05% | c.2161G>A | p.Ala721Thr | rs145548112 | missense variant | D (0) | PD (1) | 31 | 100082 | 0.015% | |
chr1:97771760 | C | A | Het | 1 | 1 | 0.02% | c.2152G>T | p.Val718Leu | NA | missense variant | T (0.24) | B (0.01) | 21.3 | NA | ||
chr1:97771837 | C | T | Het | 1 | 0 | 0.02% | c.2075G>A | p.Arg692Gln | rs375436137 | missense variant | T (0.09) | B (0.04) | 26.8 | 2412214 | 0.002% | |
chr1:97771841 | C | T | Het | 1 | 0 | 0.02% | c.2071G>T | p.Val691Leu | rs202212118 | missense variant | T (0.1) | PD (0.97) | 29.5 | 298286 | 0.015% | |
chr1:97839112 | C | T | Het | 1 | 0 | 0.02% | c.2058+5G>A | p.(?) | rs367623519 | splice region variant | 22.7 | NA | 0.005% | |||
chr1:97847973 | C | T | Het | 1 | 1 | 0.02% | c.1950G>A | p.Trp650* | NA | stop gain | 45 | NA | ||||
chr1:97915615 | G | C | Het | 1 | 0 | 0.02% | c.1905C>G | p.Asn635Lys | rs3918289 | missense variant | T (1) | B (0.02) | 1.764 | NA | 0.002% | |
chr1:97915674 | T | G | Het | 1 | 1 | 0.02% | c.1846A>C | p.Lys616Gln | rs368146607 | missense variant | D (0.01) | PD (0.96) | 26.2 | NA | 0.003% | |
chr1:97915692 | T | C | Het | 1 | 0 | 0.02% | c.1828A>G | p.Ile610Val | NA | missense variant | D (0.01) | PD (0.85) | 24.9 | NA | ||
chr1:97915724 | A | G | Het | 1 | 1 | 0.02% | c.1796T>C | p.Met599Thr | rs147601618 | missense variant | T (0.42) | B (0) | 18.83 | 550673 | 0.006% | |
chr1:97915745 | C | T | Het | 1 | 1 | 0.02% | c.1775G>A | p.Arg592Gln | rs138616379 | missense variant | D (0) | PD (0.97) | 29.8 | 554703 | 0.002% | |
chr1:97915769 | G | A | Het | 1 | 0 | 0.02% | c.1751C>T | p.Thr584Ile | NA | missense variant | T (0.12) | B (0.26) | 25.2 | NA | ||
chr1:97915777 | G | A | Het | 1 | 1 | 0.02% | c.1743C>T | p.Asp581Asp | rs555178721 | splice region variant | 11.55 | NA | 0.005% | |||
chr1:97981321 | T | A | Het | 2 | 0 | 0.03% | c.1701A>T | p.Gly567Gly | rs148372305 | synonymous variant | 9.725 | 738289 | 0.024% | |||
chr1:97981377 | C | G | Het | 1 | 0 | 0.02% | c.1645G>C | p.Ala549Pro | rs140039091 | missense variant | D (0) | PD (1) | 29.5 | NA | <0.001% | |
chr1:97981407 | C | T | Het | 1 | 1 | 0.02% | c.1615G>A | p.Gly539Arg | rs142619737 | missense variant | D (0) | PD (0.97) | 23.3 | 100093 | 0.020% | |
chr1:97981408 | G | A | Het | 1 | 0 | 0.02% | c.1614C>T | p.Ala538Ala | rs760853559 | synonymous variant | 6.617 | 298288 | 0.006% | |||
chr1:98015121 | C | T | Het | 1 | 0 | 0.02% | c.1519G>A | p.Val507Ile | rs138391898 | missense variant | T (0.93) | B (0) | 0.92 | NA | 0.001% | |
chr1:98015142 | A | G | Het | 1 | 0 | 0.02% | c.1498T>C | p.Ser500Pro | NA | missense variant | D (0) | PD (0.91) | 25.3 | NA | ||
chr1:98015280 | T | C | Het | 1 | 1 | 0.02% | c.1360A>G | p.Ile454Val | rs927463053 | missense variant | T (0.71) | B (0) | 15.44 | NA | 0.001% | |
chr1:98015291 | G | C | Het | 1 | 0 | 0.02% | c.1349C>G | p.Ala450Gly | rs72975710 | missense variant | D (0.01) | B (0.07) | 28 | 298294 | 0.002% | |
chr1:98039515 | A | G | Het | 2 | 0 | 0.03% | c.1140T>C | p.Ala380Ala | rs150759598 | synonymous variant | 9.718 | NA | 0.005% | |||
chr1:98058790 | C | T | Het | 1 | 0 | 0.02% | c.1112G>A | p.Arg371Lys | NA | missense variant | D (0.03) | B (0.07) | 25.3 | NA | ||
chr1:98058813 | G | A | Het | 1 | 1 | 0.02% | c.1089C>T | p.Phe363Phe | rs764173823 | synonymous variant | 13.76 | NA | 0.002% | |||
chr1:98058829 | C | T | Het | 1 | 0 | 0.02% | c.1073G>A | p.Arg358His | rs573299212 | missense variant | D (0) | PD (0.98) | 29.9 | NA | 0.002% | |
chr1:98058915 | T | C | Het | 1 | 0 | 0.02% | c.987A>G | p.Pro329Pro | NA | synonymous variant | 11.46 | NA | ||||
chr1:98060643 | C | T | Het | 1 | 0 | 0.02% | c.930G>A | p.Leu310Leu | NA | synonymous variant | 11 | NA | ||||
chr1:98060721 | A | C | Het | 1 | 0 | 0.02% | c.852T>G | p.Gly284Gly | NA | splice region variant | 14.32 | NA | ||||
chr1:98144657 | C | T | Het | 1 | 0 | 0.02% | c.844G>A | p.Gly282Arg | NA | missense variant | D (0) | PD (1) | 32 | NA | ||
chr1:98164964 | C | A | Het | 1 | 1 | 0.02% | c.623G>T | p.Arg208Leu | rs376073289 | missense variant | D (0) | PD (1) | 29.6 | 806173 | 0.002% | |
chr1:98164975 | G | C | Het | 1 | 0 | 0.02% | c.612C>G | p.Ser204Ser | rs768519000 | synonymous variant | 7.559 | NA | <0.001% | |||
chr1:98164986 | T | G | Het | 1 | 1 | 0.02% | c.601A>C | p.Ser201Arg | rs72549308 | missense variant | D (0) | PD (1) | 26.4 | NA | 0.003% | |
chr1:98164996 | A | G | Het | 1 | 0 | 0.02% | c.591T>C | p.Pro197Pro | rs758927521 | synonymous variant | 11.97 | 1750509 | <0.001% | |||
chr1:98165030 | T | C | Het | 1 | 0 | 0.02% | c.557A>G | p.Tyr186Cys | rs115232898 | missense variant | D (0, 0.1) | PD (0.98) | 25.5 | 100113 | 0.21% | |
chr1:98165042 | A | T | Het | 1 | 0 | 0.02% | c.545T>A | p.Met182Lys | rs779728902 | missense variant | T (0.35) | B (0.01) | 23.9 | 1321453 | 0.005% | |
chr1:98165063 | G | A | Het | 1 | 1 | 0.02% | c.524C>T | p.Ser175Leu | rs371792178 | missense variant | T (0.06) | B (0) | 18.2 | NA | 0.004% | |
chr1:98187121 | T | G | Het | 1 | 0 | 0.02% | c.428A>C | p.Tyr143Ser | NA | missense variant | T (0.39) | B (0.08) | 17.8 | NA | ||
chr1:98205947 | C | T | Het | 1 | 0 | 0.02% | c.321+1G>A | p.(?) | rs746368304 | splice donor variant | 35 | 2439928 | 0.002% | |||
chr1:98205966 | N1 | G | Het | 3 | 1 (33%) | 0.05% | c.299_302del | p.Phe100Serfs*15 | rs539032572 | *7 | frameshift variant | 33 | 495550 | 0.010% | ||
chr1:98205983 | C | G | Het | 1 | 0 | 0.02% | c.286G>C | p.Asp96His | rs773159364 | missense variant | D (0) | PD (0.99) | 25.8 | NA | <0.001% | |
chr1:98293727 | A | N2 | Het | 1 | 0 | 0.02% | c.168_175dup | p.Phe59* | NA | stop gain | NA | |||||
chr1:98348881 | G | T | Het | 1 | 1 | 0.02% | c.89C>A | p.Ser30Tyr | NA | missense variant | D (0) | PD (0.98) | 26.9 | NA | ||
chr1:98386443 | G | A | Het | 1 | 0 | 0.02% | c.36C>T | p.Ile12Ile | NA | synonymous variant | 15.25 | NA | ||||
chr1:98386447 | T | G | Het | 1 | 0 | 0.02% | c.32A>C | p.Asp11Ala | NA | missense variant | D (0) | PD (0.84) | 23.9 | NA | ||
chr1:98386452 | C | A | Het | 1 | 0 | 0.02% | c.27G>T | p.Ser9Ser | NA | synonymous variant | 13.9 | NA | ||||
chr1:98386478 | T | C | Het | 1 | 0 | 0.02% | c.1A>G | p.Met1? | rs772950053 | start lost | D (0) | B (0.23) | 24 | NA | <0.001% | |
