SV filters

On the left of the Filter View, the following filters are available for SV/CNVs and can be customised manually:

Filter set: Use the dropdown menu to select a predefined Filter set to apply to the rare variants in the sample. After selecting a Filter set, all individual filters will automatically be set to their corresponding predefined values.

Frequency: Use the sliders or the free input field to adapt frequency thresholds in gnomAD SV or the DGV Gold standard Deletions/Duplications. For each DEL/DUP, the DEL/DUP with the highest population frequency in the considered database, that completely comprises the one in the sample or has the same gene content, is annotated.

Panels: Allows you to select one or more of your labs gene Panels. Filter results show all variants located in/overlapping genes that are present in at least one of the selected panels. In order to avoid false-negative searches, Moon also takes into account synonyms, aliases, and previous names of gene names included in the panel, to perform filtering. Panels are applied for both SNVs and SVs in the Filter view.

Gene: Type in the name(s) of the gene or genes of interest, separated by a space, to filter variants. Moon takes into account every possible synonym or previous name of a gene, based on the entered search. Gene names that are not recognised are highlighted in red. Unrecognised gene names are not taken into account for filtering. Gene searches are applied for both SNVs and SVs in the Filter view.

SV type: Specify one or more SV types to be displayed as a result of filtering. In addition, the checkbox can be used to only display events that either overlap (for DEL, DUP, INS) or are expected to impact (INV, BND) exonic regions of a gene.

Segregation: The selection menu allows to only visualise variants that are de novo, biparentally inherited, or inherited from one of the parents (paternal/maternal). This is a shared Filter which, when applied, will be active for both SNVs and SVs, irrespective of whether the Filter was applied on the SNV or SV Filter view.

Zygosity and Copy number: This filter allows you to select variants of specific zygosity, deduced from the genotype defined in the uploaded VCF.

• The “compound heterozygous” option shows compound heterozygous SV/CNVs in case both parents are included in the analysis (ie. one variant should be inherited maternally, the second variant paternally), or shows potential compound heterozygous variants, in all other cases.

• For X-linked calls in males, both 1/1 and 0/1 calls are considered “hemizygous”.

The copy number is either the CN as provided in the input file, or a deduced copy number based on the combination of the SVTYPE (DEL or DUP) and the genotype.

• Heterozygous deletions are assigned CN = 1; homozygous deletions CN=0

• Heterozygous duplications are assigned CN = 3; homozygous duplications CN=4

Disorder: This field allows to enter the name of a ClinGen region (known dosage sensitive regions of interest as defined by ClinGen). All variants annotated with a ClinGen region which name contains the exact searched text will be displayed.

The checkbox allows to additionally filter on overlap with any ClinGen regions (regions with ‘sufficient’ or ‘established’ evidence). Any SV with an overlap >1 bp will be displayed if using this filter.

Region: Specify a chromosome (eg. “1”, “X”, “MT”), a region within a chromosome (eg.”1:1000-2000”), or an exact chromosomal position (eg. “1:234567) to filter on. If filtering on multiple genomic locations, these should be separated by a semicolon. This works for chromosomes (e.g. X;Y), locations (e.g. 1:4897;1:8965) or genomic ranges (e.g. 1:100-100000;2:100-100000). Any SV with an overlap >1 bp with the location/region of interest will be displayed if using this filter. This is a shared Filter which, when applied, will be active for both SNVs and SVs, irrespective of whether the Filter was applied on the SNV or SV Filter view.

Exclusion filter: This field allows you to view variants based on Moon’s reason for their exclusion from the Shortlist (e.g. insufficient phenotype overlap, gnomAD allele frequency too high, no co-segregation…).