ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.1405G>A (p.Asp469Asn)

dbSNP: rs28941778
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV000003662 SCV002058235 pathogenic Nephrotic syndrome, type 4 2022-01-03 criteria provided, single submitter clinical testing The variant has been previously reported as de novo in a similarly affected individual (PMID: 9529364, PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with WT1 related disorder (ClinVar ID: VCV000003490, PMID:1655284). A different missense change at the same codon (p.Asp469Gly, p.Asp469Tyr) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000003489,VCV000547167, PMID:22876585, PMID:1655284, PMID:10738002, PMID:24402088, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (3CNET: 0.895, PP3_P). A missense variant is a common mechanism associated with Nephrotic syndrome (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000000, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV003322746 SCV004028420 pathogenic not provided 2023-08-15 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: decreased DNA binding affinity (Pelletier et al, 1991); Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.754G>A p.D252N, c.1186G>A p.D396N, and c.1405G>A p.D469N; This variant is associated with the following publications: (PMID: 24379226, 31816618, 1338906, 1655284, 25818337, 29869118, 29294058, 9529364, 9090524, 32891756, 32053599, 34031707, 31328266, 33392118, 25077094, 20442690, Bekheirnia2021[article], 15665984)
OMIM RCV000003661 SCV000023824 pathogenic Drash syndrome 1998-04-01 no assertion criteria provided literature only
OMIM RCV000003662 SCV000023825 pathogenic Nephrotic syndrome, type 4 1998-04-01 no assertion criteria provided literature only

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