ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1447+5G>A (rs587776576)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208283 SCV000264319 pathogenic Hereditary nephrotic syndrome 2015-11-02 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV000589623 SCV000693892 pathogenic Nephrotic syndrome, type 4 2017-06-26 criteria provided, single submitter research Per OMIM: "In a patient with Denys-Drash syndrome (PMID: 1302008), with renal failure due to glomerular sclerosis associated with female external genitalia and a 46,XY karyotype, Bruening et al. (1992) identified a G-to-A transition at position +5 of the splice donor site within intron 9. It appeared that the mutation affected the alternative splice site selection at exon 9." We are reporting because we identified this variant de novo by WES in a proband with nephrotic syndrome. PS2, PS3, PM2.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000030876 SCV000731767 pathogenic Frasier syndrome 2020-01-10 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV000705142 SCV000834127 pathogenic Drash syndrome; Frasier syndrome; Wilms tumor 1; Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome 2019-11-29 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the WT1 gene. It does not directly change the encoded amino acid sequence of the WT1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with steroid-resistant nephrotic syndrome and Frasier syndrome (PMID: 9499425, 20442690, 25818337, 27719739), and has been reported to be de novo in affected individuals (PMID: 23515051, 1302008). This variant is also known as IVS9+5G>A and c.1228+5G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 3493). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this intronic change alters WT1 mRNA splicing and results in the absence of the tripeptide sequence KTS between zinc fingers 3 and 4 of the WT1 protein (PMID: 9499425, 1302008). For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostics Laboratory, M Health: University of Minnesota RCV000003665 SCV000890902 pathogenic Drash syndrome 2018-02-01 criteria provided, single submitter clinical testing
OMIM RCV000003665 SCV000023828 pathogenic Drash syndrome 1992-05-01 no assertion criteria provided literature only
OMIM RCV000030876 SCV000023839 pathogenic Frasier syndrome 1998-04-01 no assertion criteria provided literature only
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000589623 SCV000863865 pathogenic Nephrotic syndrome, type 4 2018-05-17 no assertion criteria provided clinical testing

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