NPHS2 Gene Curation
- Andrea Oza
Analytics
Gene-disease assertions not curated here (add link or write note):
Disease | Nephrotic syndrome |
|---|---|
Inheritance | Autosomal recessive |
Prevalence | 2-7 cases per 100,000 children |
Rapid or full curation? | Rapid Full |
Not in ClinGen. GenCC - Definitive/Strong by Illumina, Myriad, Invitae. Not in BabySeq. Will review HGMD variants below. | |
Clinical Validity Scoring Notes and points | HInkes 2008 PMID: 18216321 - These are patients with steroid resistant nephrotic syndrome. See supplement the following variants are NMD+ based on their HGMD nomenclature, this paper uses non-HGVS descriptors.
Bouchireb 2014 PMID: 24227627 - specific patient genotypes not provided, did not review further Sadowski 2015 PMID: 25349199 - see supplemental table 3. This isa cohort of atients with SRNS
16 POINTS GENETIC EVIDENCE, confirmed over time Functional evidence for good measure: PMID: 14701729 - podocin KO mice develop proteinuria during antenatal period and died a few days after birth from renal failure. 2 POINTS
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Clinical Validity Points Total | 18 Source: |
Clinical Validity Classification Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed | DEFINITIVE Source: 18216321, 25349199, 14701729 |
Molecular Mechanism Loss of function Gain of function Dominant negative Unknown Other | Loss of function See LOF variants scored under Clinical Validity Scoring Notes and points PMID: 18216321, 25349199, 14701729
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Penetrance Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) (list source/PMID) | INCOMPLETE OR AGE -DEPENDENT Source: 34436835 |
Age of Onset Congenital Pediatric Adolescent Adulthood Late adulthood (list source/PMID) | CONGENITAL TO ADULTHOOD |
Severity | MODERATE |
Clinical Features | proteinuria Hypoalbuminemia Edema Focal segmental glomerulosclerosis Resistant to steroid treatment Sources: PMID: 34436835 |
HPO Terms |
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Gene SOPs & Notes | LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant |
Curation Summary | The NPHS2 gene is associated with autosomal recessive nephrotic syndrome, which is characterized by proteinuria, hypoalbuminemia, edema, chronic kidney disease and end-stage-renal disease. It is typically steroid-resistant and the most prevalent histological finding is focal segmental glomerulosclerosis. The age of onset ranges from congenital to adulthood, and incomplete and/or age-dependent penetrance has been described (PMID: 34436835). |
Case ID, Curator name, Date, Jira ticket link | D-150909748-BH-3976-P-A, Andrea Oza 11.13.2023 |