Population frequency for variants missing annotation

Hello,

I'm new to whole exome sequencing, and this project looks for rare de novo variants in family trios. I followed the GATK Best Practices pipeline and then the refinement workflow to narrow down my variants to a few high confidence de novo calls. Now I'm trying to annotate them.

As I'm looking for rare variants, I'd like to annotate the VCF files and filter for MAF < .01. When I use ANNOVAR, more than half of my variants don't get annotated with population frequencies, depending on the database I use. For example, out of 70 high confidence denovo variants, only 19 are annotated when using the Population Max database, and 38 by Kaviar.

How should I treat the variants that didn't get annotated? Are they likely just errors during sequencing? Or are they rare enough that wouldn't even show up in databases, and then I should investigate them even further?

Thanks in advance,

Gustavo

annovar rare mutation

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updated 8.8 years ago by Pierre Lindenbaum

• written 8.8 years ago by gsudre •

1 answer

How should I treat the variants that didn't get annotated?

as far as I understand your variants don't exist in public databases: in consequence they should be considered as rare and you should keep them.

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written 8.8 years ago by Pierre Lindenbaum

Yes, I agree with Pierre. They are not necessarily errors in sequencing and you should keep them - they are very interesting.

They just may not have been detected in the population studies used by the programs that you have mentioned. They may also be 'private variants', i.e., only found in the individual (and most likely the family lineage) in which they were detected.

Also, don't completely discount variants with MAF > 1%. Variants at all frequencies contribute to our repective phenotypes and have roles, be them major or minor, in disease susceptibility. Take a look at Rare and common variants: twenty arguments.

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written 8.8 years ago by Kevin Blighe