高通量测序结果分析流程-BX-20170316更新.pptVIP

极强 强 中等强度 支持性 良性 / 非致病性 强力证据 支持性证据 支持性证据 中等强度证据 强证据 极强证据 群体研究 数据 MAF is too high for disorder BA1/BS1 OR observation in controls inconsistent with disease penetrance BS2 Absent in population databases PM2 Prevalence in affecteds statistically increased over controls PS4 计算机 预测 Multiple lines of computational evidence suggest no impact on gene/gene product BP4Missense in gene where only truncating cause disease BP1Silent variant with non-predicted splice impact BP7In-frame indels in repeat w/out known function BP3 Multiple lines of Computational evidence support a deleterious effect on the gene /gene product PP3 Novel missense change at an amino acid residue where a different pathogenic missense change has been seen before PM5Protein length changing variant PM4 Same amino acid change as an established pathogenic variant PS1 Predicted null variant in a gene where LOF is a known mechanism of disease PVS1 功能学 研究 Well-established functional studies show no deleterious effect BS3 Missense in gene with low rate of benign missense variants and path. missenses common PP2 Mutational hot spot or well-studied functional domain without benign variation PM1 Well-established functional studies show a deleterious effect PS3 共分离 家系研究 Nonsegregation with disease BS4 Co-segregation with disease in multiple affected family members PP1 新发突变 De novo (without paternity maternity confirmed) PM6 De novo (paternity and maternity confirmed) PS2 等位基因上的其他变异 Observed in trans with a dominant variant BP2Observed in cis with a pathogenic variant BP2 For recessive disorders, detected in trans with a pathogenic variant PM3 其他数据库 Reputable source w/out shared data = benign BP6 Reputable source = pathogenic PP5 其他研究 Found in case with an alternate cause BP5 Patient’s phenotype or FH highly specific for gene PP4 Increased segregation data 病理性 对于筛选出来的变异，原则上均应该进行Sanger测序验证后方可报告。 当遇到以下情况时应注意应用sanger测序技术对高通量测序未覆盖区域进行补充检测： 1）常染色体隐性遗传疾病，已发现一个杂合致病突变，该疾病能够很好地解释患者临床表现； 2）患者临床提示指向某一、两个特定基因时，如果尚未发现明确致病