Fig. 1: Variant interpretation pipeline. | European Journal of Human Genetics

Fig. 1: Variant interpretation pipeline.

From: Challenges for the implementation of next generation sequencing-based expanded carrier screening: Lessons learned from the ciliopathies

Fig. 1

Filtering pipeline for all variants in 118 ciliopathy-associated genes identified by whole exome sequencing in 395 healthy controls. The blue area indicates the filtering of variants to retain only high quality variants (“true calls”). SVM stands for support vector machine. The pink area describes filtering steps to determine pathogenicity of very rare variants (MAF ≤ 0.1%). Pathogenic variants are determined according to ACMG/AMP criteria. “Strong VUS” were determined as variants that are possibly damaging based on prediction tools: CADD > 20, M-CAP > 0.025, and 4 of the remaining 7 tools (SIFT, Polyphen2, FATHHM, MutationTaster, MutationAssessor, PROVEAN, LRT) predicting deleteriousness and/or previous classification in HGMD as DM or in ClinVar as LP with limited supporting information disclosed. For details please see methods.

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