Incomplete penetrance

[epouilli]

Hi,
I think a great idea would be that there is a flag or something for loci associated with incomplete penetrance. Because if a variant is inherited from a parent, it can easily be mistaken for benign without further investigation. So all variants in dominant genes that are inherited should be looked into if incomplete penetrance or variabel expression has been described in OMIM or other publications. To make an analysis easier, it would be really helpfull to flag or somehow highlight variants in genes where incomplete penetrance has been described. There is a list on the Ensembl website: https://www.ensembl.org/Homo_sapiens/Phenotype/Locations?oa=HP:0003829. Maybe the information can be exported from this list?

[hanars]

This is a good candidate for creating a gene list in seqr. You can copy the genes you provided into a gene list named "Incomplete Penetrance" and add that list to your projects, and then those genes will always show an "Incomplete Penetrance" label in search results. Gene lists can be made public, so if you would like you could make this list public so other seqr users can take advantage of this functionality as well

[epouilli]

So when we do a search with another gene panel (for example we made one for intellectual disability), if there are variants that are also in this incomplete penetrance list, they will have a label? Wow that would be great! Yes, I know that there are a lot of inherited variants from parents. We would leave the allele count and the status of the parents empty to see them. I know it is a lot of work, but it is our policy to do so. We are working with gene panels for the moment, but to make it easier to interpret those inherited variants, that label of incomplete penetrance would be so good.

[hanars]

All genes will always show all the gene lists they are in ,regardlass of search criteria

We would leave the allele count and the status of the parents empty to see them.

Manipulating VCFs to load falsified data is a violation of seqr's terms of use. This behavior is not allowed and would result in the data being deleted form seqr after one offense, and potentially your account being permanently banned form seqr if we find this happening multiple times. Therefore, the parental allele count must be accurate to what is in the VCF.
You are of course allowed to leave the parental status as "unknown", but this will result in potential disfunction/time outs in seqr searches as this is not the intended usage for seqr, and searches that return too many variants may not work.

[epouilli]

I think there is some misunderstanding. I am not doing anything to the VCFs. (I can't even access those, I am a lab supervisor, not a bio informatics). I thought just leaving the parental allele count empty in the search (inheritance section) would just be easier then filling in 0-2 for the parents to see every inheritance mode for variants found in the proband (allele count 1-2). But of course we can fill it in if that is required/better. Most of the time parents are unaffected, but sometimes they can be affected or very mild and the clinician did not notice this in the consultation. So I thought it was better than to indicate unknown.

[epouilli]

With "I know it is a lot of work" I meant interpreting inherited variants.

[hanars]

Thank you for the clarification. In general, it is best to use seqr with inheritance based searches and not by filling out specific genotypes per individual, however if you really want to you can specify allowed ACs