ClinVar Miner

Submissions for variant NM_014625.4(NPHS2):c.451+3A>T

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003562317 SCV004293847 likely pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the NPHS2 gene. It does not directly change the encoded amino acid sequence of the NPHS2 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with steroid-resistant nephrotic syndrome (PMID: 23242530, 23515051, 24969201, 30260545). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 3 and introduces a premature termination codon (PMID: 24969201). The resulting mRNA is expected to undergo nonsense-mediated decay. 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.
Baylor Genetics RCV004574090 SCV005053686 pathogenic Nephrotic syndrome, type 2 2023-12-15 criteria provided, single submitter clinical testing

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