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TheJacksonLaboratory / LIRICAL

LIkelihood Ratio Interpretation of Clinical AbnormaLities
https://thejacksonlaboratory.github.io/LIRICAL/stable
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NPHS1 #263

Closed pnrobinson closed 5 years ago

pnrobinson commented 5 years ago

https://www.ncbi.nlm.nih.gov/pubmed/?term=Three+Novel+Mutations+in+the+NPHS1+Gene+in+Vietnamese+Patients+with+Congenital+Nephrotic+Syndrome

nicolevasilevsky commented 5 years ago

I created a phenopacket for this pub: https://www.ncbi.nlm.nih.gov/pubmed/28392951

There are a number of issues: 1) They didn't report the version for the accession number (NM_004646). I remember @LCCarmody saying something about that, but wasn't sure what to do, so I just added data for v3. Is there a way to know which version # to use? I can update this if needed. 2) There were three mutations, so I added all three. Let me know if this is incorrect 3) The third mutation was a frameshift mutation, and I wasn't sure how to annotate that - so it's full of mistakes! Please let me know and I can fix it. :) 4) Regarding phenotypes 4a) we don't have a term for abnormal creatinine level, and it looks like this has come up before with LOINC2HPO and we didn't want to add this term (see: https://github.com/obophenotype/human-phenotype-ontology/issues/3783) 4b) Seems like his birth weight was normal, so I said NOT small for gestational age 4c) I added pleural effusion for multimembrane effusion

pnrobinson commented 5 years ago

There are creatinine terms for blood https://hpo.jax.org/app/browse/term/HP:0012100

pnrobinson commented 5 years ago

Patient one was reported to have three variants in the gene. The first one is described as a "polymorphism", which means that it has a high population frequency and is not considered to be disease-causing. If you look on the variant validator website, you will see that the mutation has an rs number (dbSNP entry), and if we go there we find it is very frequent: https://www.ncbi.nlm.nih.gov/snp/rs3814995 Therefore, the other two variants are considered to be the disease causing variants in this person. It is fine to enter all three variants in the app, and the simulation should be able to classify the first variant as harmless. I will add a comment in the free text field though.

pnrobinson commented 5 years ago

To get the VCF notation for c.3250_3251insG, the easiest thing is to go to variant validator and call it on

NM_004646.3:c.3250_3251insG (for hg37): https://variantvalidator.org/variantvalidation/?variant=NM_004646.3%3Ac.3250dup&primary_assembly=GRCh37&alignment=splign

THis will show that the correct HGVS notation is actually NM_004646.3:c.3250dup,NP_004637.1(LRG_693p1):p.(Val1084GlyfsTer12)

These are then the coordinates we enter for biocuration (shown further down on the variant validator page): Genomic coordinates (VCF) with respect to genome build GRCh37 19-36322580-A-AC

the snippet is then AGAGG[A/AC]CCCCCCC

pnrobinson commented 5 years ago

@nicolevasilevsky I have corrected the entry -- please have a look, it is checked in. I am closing this for now!

nicolevasilevsky commented 5 years ago

Thank you, @pnrobinson, I will review this