ABCA4 p.Gly991Val
| ClinVar: |
c.2971G>T
,
p.Gly991*
?
, not provided
c.2971G>C , p.Gly991Arg ? , not provided |
| Predicted by SNAP2: | A: N (53%), C: D (63%), D: D (66%), E: D (59%), F: D (95%), H: D (59%), I: D (75%), K: D (59%), L: D (75%), M: D (75%), N: N (53%), P: D (66%), Q: D (53%), R: D (95%), S: N (61%), T: N (53%), V: D (71%), W: D (91%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] ABCA4 gene screening by next-generation sequencing... Invest Ophthalmol Vis Sci. 2013 Oct 11;54(10):6662-74. doi: 10.1167/iovs.13-12570. Fujinami K, Zernant J, Chana RK, Wright GA, Tsunoda K, Ozawa Y, Tsubota K, Webster AR, Moore AT, Allikmets R, Michaelides M
ABCA4 gene screening by next-generation sequencing in a British cohort.
Invest Ophthalmol Vis Sci. 2013 Oct 11;54(10):6662-74. doi: 10.1167/iovs.13-12570., [PMID:23982839]
Abstract [show]
PURPOSE: We applied a recently reported next-generation sequencing (NGS) strategy for screening the ABCA4 gene in a British cohort with ABCA4-associated disease and report novel mutations. METHODS: We identified 79 patients with a clinical diagnosis of ABCA4-associated disease who had a single variant identified by the ABCA4 microarray. Comprehensive phenotypic data were obtained, and the NGS strategy was applied to identify the second allele by means of sequencing the entire coding region and adjacent intronic sequences of the ABCA4 gene. Identified variants were confirmed by Sanger sequencing and assessed for pathogenicity by in silico analysis. RESULTS: Of the 42 variants detected by prescreening with the microarray, in silico analysis suggested that 34, found in 66 subjects, were disease-causing and 8, found in 13 subjects, were benign variants. We detected 42 variants by NGS, of which 39 were classified as disease-causing. Of these 39 variants, 31 were novel, including 16 missense, 7 splice-site-altering, 4 nonsense, 1 in-frame deletion, and 3 frameshift variants. Two or more disease-causing variants were confirmed in 37 (47%) of 79 patients, one disease-causing variant in 36 (46%) subjects, and no disease-causing variant in 6 (7%) individuals. CONCLUSIONS: Application of the NGS platform for ABCA4 screening enabled detection of the second disease-associated allele in approximately half of the patients in a British cohort where one mutation had been detected with the arrayed primer extension (APEX) array. The time- and cost-efficient NGS strategy is useful in screening large cohorts, which will be increasingly valuable with the advent of ABCA4-directed therapies.
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No. Sentence Comment
56 40 c.4926C>G p.S1642R DC c.5041_5055del GTGGTTGCCATCTGC p.V1681_C1685del DC 2 41 c.4956T>G p.Y1652* DC 1 42 c.5018&#fe;2T>C Splice site DC 1 43 c.5461-10T>C DC c.6385A>G p.S2129G PDC 2 44 c.5461-10T>C DC 1 45 c.5461-10T>C DC 1 46 c.5461-10T>C DC 1 47 c.5461-10T>C DC 1 48 c.5461-10T>C DC 1 49 c.5461-10T>C DC 1 50 c.5461-10T>C DC 1 51 c.5585-1G>A Splice site DC 1 52 c.5714&#fe;5G>A Splice site DC c.6209C>G p.T2070R DC 2 53 c.5882G>A p.G1961E DC c.2686A>G p.K896E B 1 54 c.5882G>A p.G1961E DC c.3050&#fe;1G>C Splice site DC 2 55 c.5882G>A p.G1961E DC c.3392delC/3393C>G p.A1131Gfs DC 2 56 c.5882G>A p.G1961E DC c.4539&#fe;2T>G Splice site DC 2 57 c.5882G>A p.G1961E DC c.4552A>C p.S1518R DC 2 58 c.5882G>A p.G1961E DC c.5899-2delA Splice site DC 2 59 c.5882G>A p.G1961E DC 1 60 c.6079C>T p.L2027F DC c.1906C>T p.Q636* DC 2 61 c.6079C>T p.L2027F DC c.3322C>T p.R1108C DC 2 Allele 2 (p.R1108C) was APEX-false-negative 62 c.6079C>T p.L2027F DC c.3370G>T p.D1124Y DC 2 63 c.6079C>T p.L2027F DC 1 64 c.6089G>A p.R2030Q DC c.4326C>A p.N1442K DC 2 65 c.6445C>T p.R2149* DC 1 66 c.6709A>C p.T2237P DC c.5899-3_5899-2delTA Splice site DC 2 67 c.2971G>C p.G991R B c.4538A>G p.Q1513R DC 1 68 c.3602T>G p.L1201R B c.1749G>C p.K583N DC 1 69 c.3602T>G p.L1201R B c.1982_1983insG p.A662fs DC 1 70 c.3602T>G p.L1201R B c.2972G>T p.G991V DC 1 71 c.4685T>C p.I1562T B c.3289A>T p.R1097* DC 1 72 c.6320G>A p.R2107H B c.2510T>C p.L837P DC 1 73 c.6320G>A p.R2107H B c.4352&#fe;1G>A Splice site DC 1 74 c.2701A>G p.T901A B 0 75 c.3602T>G p.L1201R B 0 76 c.4283C>T p.T1428M B 0 77 c.466A>G p.I156V B 0 78 c.466A>G p.I156V B 0 79 c.4715C>T p.T1572M B 0 Putative novel variants are shown in italics.
X
ABCA4 p.Gly991Val 23982839:56:1316
status: NEW103 Hum Var Score (0-1) Site Wt CV Mt CV CV % Variation 3 c.180delG p.M61fs 1 35 ND IVS7 c.859-9T>C Splice site 1 5 Acc. 78.18 76.99 Possibly site broken (1.52) ND Possibly disease-causing 11 c.1433T>C p.I478T 1 1 Tol. B 0.007 No change ND Benign 11 c.1519G>T p.D507Y 1 20 Del. 0.01 POD 0.641 No change 1/13006 dbSNP (rs148234178) 12 c.1749G>C p.K583N 1 68 Del. 0.04 POD 0.893 Acc. 66.17 37.22 Site broken (43.75) 1/13006 dbSNP (rs145265791) 14 c.1982_ 1983insG p.A662fs 1 69 ND 15 c.2297G>T p.G766V 1 1 Tol. NA POD 0.557 Don. 69.18 42.34 Site broken (38.79) ND 15 c.2345G>A p.W782* 1 3 ND 16 c.2510T>C p.L837P 1 72 Tol. NA POD 0.905 No change ND 16 c.2568C>A p.Y856* 1 5 ND 18 c.2686A>G p.K896E 1 53 Tol. NA B 0.002 ND Benign 20 c.2942C>T p.P981L 1 19 Del. 0.00 POD 0.813 No change 1/13006 dbSNP (rs147826775) 20 c.2972G>T p.G991V 1 70 Del. NA PRD 0.998 Donor 64.62 91.45 New site (41.53) ND IVS20 c.3050&#fe;1G>C Splice site 1 54 Acc. 86.43 57.49 Site broken (33.49) ND IVS21 c.3191-1G>T Splice site 1 26 Acc. 94.38 65.44 WT site broken (30.67) ND 22 c.3289A>T p.R1097* 1 71 ND 22 c.3299T>A p.I1100N 1 23 Del. NA PRD 0.986 No change ND 23 c.3370G>T p.D1124Y 1 62 Del. NA PRD 0.998 No change ND 23 c.3392delC/ 3393C>G p.A1131Gfs 1 55 ND 23 c.3398T>C p.I1133T 1 27 Del. NA B 0.100 No change ND Possibly disease-causing 27 c.4070C>A p.A1357E 1 28 Del. NA PRD 0.94 Acc. 40.92 69.86 New site (&#fe;70.74) ND IVS30 c.4539&#fe;2T>G Splice site 1 56 Don. 79.18 52.35 WT site broken (33.89) ND 31 c.4552A>C p.S1518R 1 57 Del. NA POD 0.871 Acc. 76.3 47.36 Site broken (37.94) ND 31 c.4634G>A p.S1545N 2 21, 25 Tol. NA B 0.253 Acc. 80.04 51.1 Site broken (36.16) ND 5. Continued Exon/ IVS DNA Change Protein Change/ Effect N of Alleles Identified Pt SIFT Polyphen2 HSF Matrix Allele Freq. by EVS Reference Comments Pred. Tol. Index (0-1) Pred.
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ABCA4 p.Gly991Val 23982839:103:825
status: NEW