ABCA7 p.Glu2108Lys
| Predicted by SNAP2: | A: N (61%), C: N (57%), D: N (78%), F: N (57%), G: N (57%), H: N (66%), I: N (66%), K: N (78%), L: N (61%), M: N (57%), N: N (66%), P: N (61%), Q: N (66%), R: N (57%), S: N (82%), T: N (72%), V: N (82%), W: D (63%), Y: N (61%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: N, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D, |
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[hide] Rare-variant extensions of the transmission disequ... Am J Hum Genet. 2014 Jan 2;94(1):33-46. doi: 10.1016/j.ajhg.2013.11.021. Epub 2013 Dec 19. He Z, O'Roak BJ, Smith JD, Wang G, Hooker S, Santos-Cortez RL, Li B, Kan M, Krumm N, Nickerson DA, Shendure J, Eichler EE, Leal SM
Rare-variant extensions of the transmission disequilibrium test: application to autism exome sequence data.
Am J Hum Genet. 2014 Jan 2;94(1):33-46. doi: 10.1016/j.ajhg.2013.11.021. Epub 2013 Dec 19., [PMID:24360806]
Abstract [show]
Many population-based rare-variant (RV) association tests, which aggregate variants across a region, have been developed to analyze sequence data. A drawback of analyzing population-based data is that it is difficult to adequately control for population substructure and admixture, and spurious associations can occur. For RVs, this problem can be substantial, because the spectrum of rare variation can differ greatly between populations. A solution is to analyze parent-child trio data, by using the transmission disequilibrium test (TDT), which is robust to population substructure and admixture. We extended the TDT to test for RV associations using four commonly used methods. We demonstrate that for all RV-TDT methods, using proper analysis strategies, type I error is well-controlled even when there are high levels of population substructure or admixture. For trio data, unlike for population-based data, RV allele-counting association methods will lead to inflated type I errors. However type I errors can be properly controlled by obtaining p values empirically through haplotype permutation. The power of the RV-TDT methods was evaluated and compared to the analysis of case-control data with a number of genetic and disease models. The RV-TDT was also used to analyze exome data from 199 Simons Simplex Collection autism trios and an association was observed with variants in ABCA7. Given the problem of adequately controlling for population substructure and admixture in RV association studies and the growing number of sequence-based trio studies, the RV-TDT is extremely beneficial to elucidate the involvement of RVs in the etiology of complex traits.
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259 Bioinformatic Evaluation and Frequencies of Rare Missense Variants within ABCA7 Chr19 Position Nucleotide Substitutiona PhyloPb GERPc Amino Acid Substitution PolyPhen-2 SIFT MutationTaster Mutation Assessor Transmitted/ Non-transmitted Events dbSNP rsID NHLBI-ESP EA MAFd NHLBI-ESP AA MAFd 1,043,788e c.995G>A 2.90 4.33 p.Gly332Glu Probably damaging Damaging Polymorphism Functional, medium 1/0 NA NA NA 1,045,109 c.1324G>A 0.28 2.54 p.Gly442Arg Possibly damaging Tolerated Polymorphism Nonfunctional, low 1/0 NA NA NA 1,046,317 c.1534C>G 0.04 1.11 p.Arg512Gly Benign Tolerated Polymorphism Neutral 1/0 NA 0.0001 0 1,050,996 c.2629G>Af 1.18 2.59 p.Ala877Thr Benign Tolerated Polymorphism Nonfunctional, low 5/1 rs74176364 0.006 0.003 1,051,481 c.2858C>A 4.96 4.43 p.Ala953Asp Probably damaging Damaging Disease-causing Functional, high 1/0 NA NA NA 1,057,343 c.4795G>Af 1.58 3.65 p.Val1599Met Probably damaging Damaging Polymorphism Functional, medium 2/0 rs117187003 0.004 0.0009 1,058,883 c.5344C>T 1.58 3.14 p.Arg1782Trp Probably damaging Damaging Disease-causing Functional, medium 1/0 NA 0.0003 0 1,059,056 c.5435G>Af 1.28 0.81 p.Arg1812His Benign Damaging Polymorphism Neutral 3/1 rs114782266 0.005 0.07 1,062,248 c.5648C>T 4.87 3.61 p.Thr1883Met Probably damaging Damaging Disease-causing Functional, high 1/0 NA 0 0.0002 1,065,305 c.6322G>Af 2.08 3.73 p.Glu2108Lys Benign Tolerated Polymorphism Functional, medium 1/0 rs139706726 0.0002 0 a cDNA position is based on reference sequence NM_019112.3.
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ABCA7 p.Glu2108Lys 24360806:259:1363
status: NEW