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EX116_VA079_trio EX110_VA073 affected , the other two are healthy Result files: /users/GD/projects/HumanDisease/Vall_Hebron/analysis_ediva1.0/ataxia/EX1 16_VA079_trio Compound inheritance candidate MYH7B The compound variants are o Frameshift indel and a non damaging SNV on one side o C>T SNP with 35 CADD score [damaging] on the other side o These two variants may impair the function of MYH7B MYH7B (Myosin, Heavy Chain 7B, Cardiac Muscle, Beta) is a Protein Coding gene. Diseases associated with MYH7B include left ventricular noncompaction LVNC and myotonic disease. From https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-891 : o LVNC has been reported in patients with different types of NMDs, including dystrophinopathy, laminopathy, zaspopathy, myotonic dystrophy, Barth syndrome, Friedreich ataxia, Charcot-MarieTooth disease, and metabolic and mitochondrial disorders [27,28]. It shows String connections to ataxia - related genes: o Other compound genes Gene PLEKHA7 has two damaging SNPs and it is related http://neurosciencenews.com/mirna-cancer-cell-reprogramming-2491/ to be an importat gene against cancer which could be impaired in this sample Recessive candidate MLC1 [variant is actually common] This candidate is related to ataxia because it is causal for Megalencephalic Leukoencephalopathy with Subcortical Cysts o http://www.cell.com/ajhg/abstract/S0002-9297(07)61409-8 o “Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor functions with ataxia, and spasticity, eventuating in mental decline. “ Also in OMIM identified with MLC1 gene and it is characterized by ataxia o http://www.omim.org/entry/604004 A familial case of MLC1 mutated in patients with MLC disease o http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424803/ The main problem here is the low coverage we have for the affected patient with a depth of only 6 [all mutated] The variant is a nonframeshift insertion, but it is actually common in exomes around 6% in Europeans non Finnish [0.8% homozygous] In our ExAC values it returns ‘0’ because it was not included but in the ExAC browser it is shown to be > 4% in the population with 233 homozygous in the Non finnish European sample set, http://exac.broadinstitute.org/variant/22-50502469-AAGCACCCCCACCCCACAGGCCACTCACCTCCCCG We did not include this because the variant is not of top quality in ExAC set (VQSR Tranche INDEL 99.00 to 99.50 ) Variants Chr Position Reference Alteration Function(Refseq) Gene(Refseq) ExonicFunction(Refseq) dbsnpIdentifier EurEVSFrequency TotalEVSFrequency Eur1000GenomesFrequ ency Total1000GenomesFreq uency SIFTScore polyphen2 MutAss 22 50502469 A AGCACCCCCACC CCACAGGCCACT CACCTCCCCG exonic MLC1 nonframeshift insertion rs11568189 0 0 20 33584197 C 20 33584521 G 20 33588210 G T exonic MYH7B nonsynonymous SNV rs61745051 0.01442531403 0.01031562779 A exonic MYH7B nonsynonymous SNV NA 0 0 GGA exonic MYH7B frameshift insertion NA 0 0 0 0.01790 0 0 0 NA NA NA 0.00519 NA 0.522 1.975 0 NA 0.237 0.69 0 NA NA NA Condel Cadd1 Cadd2 Eigen_raw Eigen_Phred ABB_score ExAC_adjusted_AF ExAC_NFE SimpleTandemRepeatRe gion SimpleTandemRepeatLe ngth EX116_VA079 DP REF ALT EX118_VA081 DP REF ALT EX117_VA080 DP REF ALT NA NA NA NA NA 0 0.06 0.06 0.514 7.631988 35 0.368988 4.15695 0.112 0.0119868 0.0179415 0.207 2.012553 16.29 -0.688883 0.831463 0.1123 0.000263002 0.000200142 NA NA NA NA NA 0 0 0 NA NA NA NA NA 1/1 6 0 6 0/1 18 13 5 0/1 27 17 9 NA 0/1 97 47 50 0/0 169 168 1 0/1 124 76 48 NA 0/1 47 28 19 0/1 55 29 26 0/0 68 68 0 NA 0/1 46 21 21 0/1 58 31 20 0/0 57 55 0