ABCMdb

PMID: 21911583

Zernant J, Schubert C, Im KM, Burke T, Brown CM, Fishman GA, Tsang SH, Gouras P, Dean M, Allikmets R
Analysis of the ABCA4 gene by next-generation sequencing.
Invest Ophthalmol Vis Sci. 2011 Oct 31;52(11):8479-87. doi: 10.1167/iovs.11-8182., [PubMed]

Sentences

No. Mutations Sentence Comment

17 ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Leu541Pro Several studies have identified frequent "ethnic group-specific" ABCA4 alleles, such as the c.2588Gb0e;C variant resulting in a dual effect, p.G863A/delG863, as a founder mutation in Northern European patients with STGD17 and a complex allele (two variants on the same chromosome), p.L541P/A1038V, in both STGD1 and CRD patients of German origin (Fig. 2B).3,8 Complex ABCA4 alleles are not uncommon in STGD1.9 In fact, they are detected in approximately 10% of all STGD patients.10 Allelic heterogeneity has substantially complicated genetic analyses of ABCA4-associated retinal disease. Login to comment 38 ABCA4 p.Val767Asp ABCA4 p.Tyr245* Fundus autofluorescence image of the left eye of patient 3032 harboring ABCA4 variants c.2300Tb0e;A (p.V767D) and c.735Tb0e;G (p.Y245*). Login to comment 64 ABCA4 p.Arg1108Cys Mother is a carrier of a frequent c.3322Cb0e;T (p.R1108C) mutation. Login to comment 66 ABCA4 p.Leu541Pro (B) An example of a pedigree segregating a frequent complex ABCA4 allele [c.1622Tb0e;C; 3113Cb0e;T] (p.L541P;A1038V), in which either mutation separately can cause the disease. Login to comment 68 ABCA4 p.Asn965Ser ABCA4 p.Thr1428Met (C) An example of a pedigree segregating a complex allele in which one variant (c.2894Ab0e;G, p.N965S) causes disease and the other, c.4283Cb0e;T, p.T1428M, is a benign polymorphism, although it was originally described as a rare mutation in patients of European descent. Login to comment 69 ABCA4 p.Ala1219Pro The new c.3655Gb0e;C, p.A1219P variant was detected by NGS. Login to comment 120 ABCA4 p.Phe655Cys ABCA4 p.Cys748Tyr ABCA4 p.Pro62Ser ABCA4 p.Trp31Arg ABCA4 p.Thr2240Ala ABCA4 p.Ala801Thr ABCA4 p.Ala1219Pro ABCA4 p.Val1393Ile ABCA4 p.Tyr106* ABCA4 p.Tyr1557Cys ABCA4 p.Asp2102Glu ABCA4 p.Asn1442Lys ABCA4 p.Gln636* ABCA4 p.Asp1093Glu ABCA4 p.Glu1271Gly ABCA4 p.His1406Arg ABCA4 p.Gln623Arg ABCA4 p.Arg1489Ser ABCA4 p.Met1882Ile ABCA4 p.Leu257Arg ABCA4 p.Thr1117Ile ABCA4 p.Leu1580* ABCA4 p.Lys1069Glu ABCA4 p.Met659Ile ABCA4 p.Lys1547* ABCA4 p.Asn582Ser ABCA4 p.Asn965Tyr ABCA4 p.Trp41* ABCA4 p.Thr1726Asn ABCA4 p.Gly1050Ser ABCA4 p.Phe1416Leu ABCA4 p.Phe418Ser ABCA4 p.Gln1713Arg ABCA4 p.Arg511Cys Novel Variants Detected by NGS in the ABCA4 Gene and Results of Analysis Using Bioinformatics Software Nucleotide Change Protein Splicing Score Original Splicing Score for New Variant Average Difference Polyphen SIFT SpliceSite Finder-like Gene Splicer SpliceSite Finder-like Gene Splicer c.91Tb0e;C p.W31R 0 0 0 0 0 Probably damaging (0.999) W c.184Cb0e;T p.P62S 0 0 0 0 0 Probably damaging (0.999) P c.770Tb0e;G p.L257R 0 0 0 0 0 Possibly damaging (0.308) m i F L c.1253Tb0e;C p.F418S 0 0 0 0 0 Probably damaging (0.999) F c.1531Cb0e;T p.R511C 0 0 0 0 0 Probably damaging (1.000) R c.1745Ab0e;G p.N582S 0 0 0.74 0.82 77.8 Probably damaging (0.894) d K N c.1868Ab0e;G p.Q623R 0 0.24 0 0 12.1 Probably damaging (0.937) Q c.1964Tb0e;G p.F655C 0 0 0 0 0 Probably damaging (0.999) F c.1977Gb0e;A p.M659I 0 0 0.75 0.85 79.8 Probably damaging (0.999) M c.2243Gb0e;A p.C748Y 0 0 0 0 0 Probably damaging (0.928) g S A C c.2401Gb0e;A p.A801T 0 0 0 0 0 Probably damaging (0.98) A c.2893Ab0e;T p.N965Y 0 0 0 0 0 Probably damaging (0.999) N c.3148Gb0e;A p.G1050S 0 0 0 0 0 Possibly damaging (0.786) G c.3205Ab0e;G p.K1069E 0 0 0 0 0 Probably damaging (0.993) K c.3279Cb0e;A p.D1093E 0 0 0 0 0 Probably damaging (0.99) D c.3350Cb0e;T p.T1117I 0 0 0 0 0 Probably damaging (0.995) T c.3655Gb0e;C p.A1219P 0.77 0 0.74 0 1.5 Probably damaging (0.991) A c.3812Ab0e;G p.E1271G 0.8 0.35 0.71 0 21.8 Probably damaging (0.995) E c.4177Gb0e;A p.V1393I 0 0 0 0 0 Benign (0.000) VI c.4217Ab0e;G p.H1406R 0 0 0 0 0 Probably damaging (0.986) r p q a t k e g n S D H c.4248Cb0e;A p.F1416L 0.79 0.1 0.79 0.1 0.27 Probably damaging (0.891) F c.4326Cb0e;A p.N1442K 0 0 0 0 0 Possibly damaging (0.374) a g d s T N c.4467Gb0e;T p.R1489S 0.85 0.43 0.78 0.24 12.8 Benign (0.047) p h l s n a e T Q K R c.4670Ab0e;G p.Y1557C 0.85 0.13 0.80 0 8.8 Probably damaging (0.999) f W Y c.5138Ab0e;G p.Q1713R 0 0 0 0 0 Probably damaging (0.997) Q c.5177Cb0e;A p.T1726N 0 0 0 0 0 Probably damaging (0.880) s A T c.5646Gb0e;A p.M1882I 0 0 0.75 0 37.4 Probably damaging (0.999) M c.6306Cb0e;A p.D2102E 0 0 0 0 0 Probably damaging (0.99) D c.6718Ab0e;G p.T2240A 0 0 0 0 0 Probably damaging (0.991) T c.160af9;2Tb0e;C 0.81 0.86 0.79 0 44.4 c.1240afa;2Ab0e;G 0.82 0.81 0 0 81.5 c.2382af9;1Gb0e;A 0.79 0.64 0 0 71.7 c.2919afa;2Ab0e;G 0.9 0.92 0 0 90.9 c.3522af9;5delG 0.87 0.57 0 0.18 63 c.3523afa;1Gb0e;A 0.9 0.89 0 0 89 Splice site shift of 1 bp c.3814afa;2Ab0e;G 0.91 0.9 0 0 90.6 c.4352af9;1Gb0e;A 0.74 0.82 0 0 78 c.4635afa;1Gb0e;T 0.86 0.89 0 0 87.5 New splice site 7 bp downstream c.5312af9;1Gb0e;A 0.81 0.91 0 0 86.1 c.5836afa;2Ab0e;C 0.89 0.87 0 0 88 c.6387afa;1Gb0e;T 0.77 0.87 0 0 82 c.6479af9;1Gb0e;A 0.82 0.87 0 0 85 c.6479af9;1Gb0e;C 0.82 0.31 0 0 56.6 c.1100afa;6Tb0e;A 0 0 0.9 0.93 91.6 Creates new splice site c.351_352delAG p.S119fs Frameshift c.564delA p.E189Cfs Frameshift c.885delC p.L296Cfs Frameshift c.1374delA p.T459Qfs Frameshift c.3543delT p.K1182Rfs Frameshift c.3846delA p.G1283Dfs Frameshift c.4734delG p.L1580* Stop codon c.5932delA p.T1979Qfs Frameshift c.6317_6323del p.R2107_ GCCGCAT M2108delfs Frameshift c.121Gb0e;A p.W41* Stop codon c.318Tb0e;G p.Y106* Stop codon c.1906Cb0e;T p.Q636* Stop codon c.4639Ab0e;T p.K1547* Stop codon For SpliceSiteFinder and GeneSplicer, 1 is the highest score for splice site activity and 0 is the lowest. Login to comment 127 ABCA4 p.Gly1961Glu ABCA4 p.Arg2106Cys ABCA4 p.Pro1486Leu Three ABCA4 mutations in three different samples identified by sequencing-p.P1486L, p.G1961E, and p.R2106C-represented ABCA4 array false negatives. Login to comment 130 ABCA4 p.Gly1961Glu ABCA4 p.Arg2149* From 53 samples in which the combined APEX/NGS analysis had detected two mutations, only two samples carried the same two mutations-p.G1961E and p.R2149*. Login to comment 136 ABCA4 p.Val1393Ile ABCA4 p.Arg1489Ser 11 Deep Sequencing of the ABCA4 Gene doi:10.1167/iovs.11-8182/-/DCSupplemental), including two novel rare variants p.V1393I and p.R1489S (both detected once) that were predicted to be tolerated. Login to comment 145 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro The best known example from this category in ABCA4 is the c.5461-10Tb0e;C variant in intron 38, which is the third most frequent variant (found in 7.1% of STGD1 patients) after the p.G1961E and p.L541P/A1038V mutations in our study. Login to comment