varfish-org / mehari

VEP-like tool for sequence ontology and HGVS annotation of VCF files
MIT License
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Factor V Leiden Mutation missing because of Transcript liftover #412

Open einicke opened 3 months ago

einicke commented 3 months ago

Describe the bug Factor 5 Leiden Mutation c.1601G>A p.Arg534Gln is the reference in hg37:chr1:169,519,049-T-T, this was fixed in hg38:chr1:169549811-C-T.

The Mane Transcript of F5 NM_000130.5 (and also the older NM_000130.4) were uptated earlier and have the correct G as a reference.

In Varfish, the heterozygous variant is first annotated as hg37:chr1:169,519,049-T-C and then predicted as NM_000130.4:c.1601G>G in the result table. The ClinVar linkout also leads to the benign NM_000130.5(F5):c.1601= (p.Arg534=).

Homozygous mutations will be therefore missed at all and heterozygous variants will be classified as benign.

Expected behavior Variant should be called correctly as c.1601G>A p.Arg534Gln