ClinVar Miner

Submissions for variant NM_144696.6(AXDND1):c.3032-1891_3032-1890del (rs749740335)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000730521 SCV000858264 pathogenic not provided 2017-12-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169166 SCV000919905 pathogenic Idiopathic nephrotic syndrome 2018-10-01 criteria provided, single submitter clinical testing Variant summary: NPHS2 c.855_856delAA (p.Arg286ThrfsX17) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 6.5e-05 in 275798 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in NPHS2 causing Nephrotic Syndrome, Type 2 (6.5e-05 vs 0.0018), allowing no conclusion about variant significance. c.855_856delAA has been reported in the literature in multiple individuals affected with Steroid Resistant Nephrotic Syndrome. These data indicate that the variant is very likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Myriad Women's Health, Inc. RCV000169166 SCV001194121 pathogenic Idiopathic nephrotic syndrome 2020-01-03 criteria provided, single submitter clinical testing NM_014625.2(NPHS2):c.855_856delAA(R286Tfs*17) is classified as pathogenic in the context of NPHS2-related nephrotic syndrome. Sources cited for classification include the following: PMID 11805166, 18823551, 19406966, 24742477 and 15327385. Classification of NM_014625.2(NPHS2):c.855_856delAA(R286Tfs*17) is based on the following criteria: The variant causes a premature termination codon that is not expected to be targeted by nonsense-mediated mRNA decay; however, literature evidence strongly supports pathogenicity. Please note: this variant was assessed in the context of healthy population screening.
Invitae RCV000730521 SCV001231677 pathogenic not provided 2019-12-18 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NPHS2 gene (p.Arg286Thrfs*17). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 98 amino acids of the NPHS2 protein. This variant is present in population databases (rs749740335, ExAC 0.01%). This variant has been observed to be homozygous or compound heterozygous in several individuals with steroid resistant nephrotic syndrome (PMID: 18823551, 20947785, 24509478, 21355056, 11805166). ClinVar contains an entry for this variant (Variation ID: 188823). For these reasons, this variant has been classified as Pathogenic.
Cavalleri Lab, Royal College of Surgeons in Ireland RCV001171356 SCV001328303 likely pathogenic Chronic kidney disease 2020-05-28 criteria provided, single submitter research PVS1, PM3
OMIM RCV000169166 SCV000025877 pathogenic Idiopathic nephrotic syndrome 2000-04-01 no assertion criteria provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003813 SCV001162264 pathogenic Nephrotic range proteinuria no assertion criteria provided research
Natera, Inc. RCV001273611 SCV001456811 pathogenic Steroid-resistant nephrotic syndrome 2020-09-16 no assertion criteria provided clinical testing
GeneDx RCV000730521 SCV001805111 likely pathogenic not provided 2020-12-17 no assertion criteria provided clinical testing Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 98 amino acids are lost and replaced with 16 incorrect amino acids (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 33226606, 33144682, 31589614, 32581362, 19145239, 17699384, 10742096, 11805166, 14978175, 25949442, 30655312, 30260545, 15322893, 15253708, 15327385, 15769810, 24227627, 30295827, 18823551, 12464671)

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