ClinVar Miner

Submissions for variant NM_144696.6(AXDND1):c.3032-1887G>A (rs780761368)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000681863 SCV000842935 pathogenic not provided 2019-05-31 criteria provided, single submitter clinical testing The best available variant frequency is uninformative because there are too few occurrences in population data. Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein. Occurs in three or more cases with a recessive pathogenic variant in the same gene.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781678 SCV000919906 likely pathogenic Idiopathic nephrotic syndrome 2021-02-06 criteria provided, single submitter clinical testing Variant summary: NPHS2 c.851C>T (p.Ala284Val) results in a non-conservative amino acid change located in the Band 7 domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249998 control chromosomes. c.851C>T has been reported in the literature in multiple individuals affected with Nephrotic Syndrome, Type 2, a disorder characterized clinically by childhood onset of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation, resistance to sterpoid treatment and progression to end stage renal failure (example, Tsukaguchi_2002, Santin_2011, Karle_2002). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2)/likely pathogenic(n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000681863 SCV001231507 likely pathogenic not provided 2020-08-25 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 284 of the NPHS2 protein (p.Ala284Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs780761368, ExAC 0.002%). This variant has been observed in individual(s) with steroid-resistant nephrotic syndrome (PMID: 11805166, 29982877, 23515051, 23349334). ClinVar contains an entry for this variant (Variation ID: 562398). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Gharavi Laboratory,Columbia University RCV000681863 SCV000809342 pathogenic not provided 2018-09-16 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.