Figure 1

Variant filtering and classification process. Amidst 694 rare and functional or known pathogenic variants found in our population, 107 variants were classified as benign (B), likely benign (LB), or a variant of uncertain significance (VUS) during the filtering process (filtered variants). Firstly, 82 variants were classified as B, LB, or conflicting between B, BL, and VUS based on their ClinVar classification. Next, variants in noncoding regions and synonymous variants that were not present in ClinVar or were classified as VUS in ClinVar were assigned VUS status (21 variants). We added 12 variants to the classification group since they are known pathogenic variants, frequent in control populations and cancer patients. The resulting 603 variants were classified manually according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG) standards and guidelines for the interpretation of sequence variants (ACMG guidelines). We classified 603 variants into five categories: pathogenic (P), likely pathogenic (LP), variant of uncertain significance, and likely benign or benign. Six variants were classified as benign, 127 were likely benign, 396 were VUS, of which ten were conflicting between B/LB and P/LP and there was not enough data to classify the remaining 381 variants into either B/LB or P/LP categories. Lastly, 14 variants were likely pathogenic and 60 were classified as pathogenic.