ClinVar Miner

Submissions for variant NM_144696.6(AXDND1):c.3032-1904C>T (rs200482683)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000190610 SCV000245644 likely pathogenic Nephrotic syndrome, idiopathic, steroid-resistant 2014-05-12 criteria provided, single submitter clinical testing The p.Val290Met variant in NPHS2 has been reported in at least 5 individuals with steroid-resistant nephrotic syndrome. Two individuals were homozygous for this variant (Reiterova 2012, Kerti 2013) and three were compound heterozygotes (Karle 2002, Skalova 2010, Kerti 2013). The variant has been identified in 0.012% (1/8600) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/) Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational analyses (biochemical amino acid properties, conservation, PolyPhen2) do not provide strong support for or against an impact to the protein. In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significance.
Counsyl RCV000190610 SCV000485288 pathogenic Nephrotic syndrome, idiopathic, steroid-resistant 2016-07-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588976 SCV000699386 pathogenic Idiopathic nephrotic syndrome 2016-11-10 criteria provided, single submitter clinical testing Variant summary: The NPHS2 c.868G>A (p.Val290Met) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 9/114830 control chromosomes at a frequency of 0.0000784, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPHS2 variant (0.0017678). This variant has been reported in numerous patients with NSPH2. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000190610 SCV000893930 likely pathogenic Nephrotic syndrome, idiopathic, steroid-resistant 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000190610 SCV000914365 pathogenic Nephrotic syndrome, idiopathic, steroid-resistant 2019-01-11 criteria provided, single submitter clinical testing The NPHS2 c.868G>A (p.Val290Met) missense variant is reported in six studies in which it is found in a total of 11 individuals affected with steroid-resistant nephrotic syndrome, including in five individuals in a compound heterozygous state, in three affected individuals in a homozygous state and in three individuals in a heterozygous state (Karle et al. 2002; Skálová et al. 2010; Reiterová et al. 2012; Kerti et al. 2013; Lipska et al. 2013; Bińczak-Kuleta et al. 2014). The p.Val290Met variant was absent from 700 control chromosomes and is reported at a frequency of 0.0002412 in the European (non-Finnish) population of the Genome Aggregation Database. Although this variant has been observed in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Based on the collective evidence, the p.Val290Met variant is classified as pathogenic for steroid-resistant nephrotic syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000114358 SCV000147970 risk factor Nephrotic syndrome, type 2, susceptibility to 2013-05-01 no assertion criteria provided literature only
Gharavi Laboratory,Columbia University RCV000681842 SCV000809319 pathogenic not provided 2018-09-16 no assertion criteria provided research

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