What are the responsibilities of a PI working with the SGFS?
- Consult with her/his IRB to determine if secondary variant analysis is routine or if participants can opt-out.
- Provide staff who are adequately trained to perform the informed consent for secondary findings and who can enter CRIS orders.
- Ensure correct samples are sent to SGFS. This includes ensuring that all data sent to the SGFS come from research participants who have appropriately consented to secondary variant analysis and return.
- Coordinate communication with research participants whom do not have a secondary finding to convey that the analysis has been completed.
Please read the Guidance document to understand your full responsibilities.
How do I consent my participants to receiving secondary findings?
The SGFS requires that protocols include appropriate language for the evaluation and return of secondary findings. Participants must understand that their samples will be evaluated by our service and that they may be re-contacted at a later time. We have provided some suggested language to incorporate into protocols and consent forms.
As with all parts of your consent form, it is crucial you talk with your participants about secondary findings analysis. Below are some practical points to emphasize during your consent conversation:
- The purpose of annotating for and returning secondary findings is to improve outcomes for participants - most participants are very comfortable with this idea, even if seems like initially unwelcome information
- Secondary variants will only be present in a small fraction of your participants
- Not having any secondary findings present does not mean that a person has a "clean genetic bill of health" - they can still get any of the diseases associated with the genes we look at in our analysis
- Participants who have secondary findings will receive genetic counseling about what the finding means for them and their family members and what next steps to take
In our experience, the wait between told that there is a possible secondary finding and actually getting that finding confirmed can be very anxiety provoking. To mitigate this, the SGFS staff member who will contact your participant to coordinate getting a confirmatory sample will not know the participant's possible finding. They will simply state that there is a potential genetic finding that your team would like to learn more about and that this will require submission of a new sample. When consenting participants, it may be helpful to emphasize that the participant may be re-contacted in the future to provide another sample for any number of reasons, not solely to confirm a potential secondary finding.
What type of data does the SGFS accept?
The SGFS will only accept a de-identified single file in variant call format (.vcf). Please note files must be restricted to the coding/splice regions of the genes included in the ACMG list of genes for return of secondary variants. See below for additional details:
VCF (Variant Call Format) file requirements
- VCF file
- If there is only one sample, a single VCF file for the patient is acceptable.
- If there are more than one sample, a single multi-sample VCF for all samples to be analyzed is acceptable. Please do not send individual VCF files.
- Bioinformatics pipeline
- We strongly recommend the VCF file to be generated using the GATK best practices pipeline.
- For other pipelines, please check recommended QC filter to exclude low quality variants.
- Reference genome
- GRCh37, hg19 or other variation of reference human genome GRCh37/hg19 (eg. b37) is acceptable.
- Please note that hg38 is not accepted and will not be processed. If the VCF file is in hg38 coordinates, 1) lift over the coordinates to GRCh37/hg19, then 2) proceed to “pre-processing a VCF file” section.
Pre-processing a VCF file
VCF file must be restricted to ACMG 59 genes. Coordinates are provided as a BED file ACMG_genes_txt_GRCh37_sort_merge_padded.bed. Please check the compatibility of chromosome notations (i.e. “chr1” vs “1”) when using the BED file for subsetting the VCF file.
Filter the VCF file to only include high quality (“PASS”) variants. If GATK pipeline was not used, please filter variants to only include high quality variants suggested by the method used.
Last updated: March 23, 2021