Import some variants as annotations

[Nicklas Nordborg]

If we find one or more variants in a sample that belongs to a predefined list of "important" variants this information should be imported after the variant calling as an annotation in BASE.

The predefined list of variants should probably be a VCF file with specified chr:pos:ref>alt and some extra information that we can use. We should at least have the GENE name and match that to an annotation type in BASE. For example, if we have a variant:

#CHROM	POS		ID	REF	ALT	QUAL	FILTER	INFO	FORMAT
chr3	179234297	.	A	G	.	.	GENE=PIK3CA;AA=H1047R

we should import chr3:179234297:A>G to the PIK3CA_Variants annotation (and possibly also the AA tag).

NOTE! The idea is to run this scan/import at the end of the regular variant calling pipeline. To import the same information for existing variant call items, a special script that creates a tab-separated text file (or similar) is needed. The text file can then be imported with the regular annotation importer plug-in.

The list of interesting genes:

• PIK3CA
• AKT1
• SF3B1
• GATA3
• ERBB2
• TP53
• FOXA1
• CDH1
• MAP3K1
• PTEN
• KMT2C
• TBX3
• CBFB
• ARID1A
• RNF213
• PLEC
• RUNX1
• TRPS1
• ARHGAP35
• NFIC

The ESR1 gene is also interesting but here we should only import variants that are known drug resistance mutations.

• chr6:152011697:G>C E380Q
• chr6:152011733:G>A V392I
• chr6:152061020:ATGG>A V422del
• chr6:152094402:T>C S463P
• chr6:152098775:G>A V533M
• chr6:152098779:T>A V534E
• chr6:152098785:TC>AG L536Q
• chr6:152098785:T>C L536P
• chr6:152098785:T>G L536R
• chr6:152098787:T>G Y537D
• chr6:152098787:T>A Y537N
• chr6:152098788:A>C Y537S
• chr6:152098791:A>G D538G

The original list had some more variants, but they turned out to have unknown genomic positions.