ClinVar Miner

Submissions for variant NM_000278.5(PAX2):c.44-12_44-8dup

dbSNP: rs1845364215
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195632 SCV001366031 uncertain significance not specified 2019-11-13 criteria provided, single submitter clinical testing The c.44-12_44-8dup (NM_003990.3) variant in PAX2 has not been previously reported in individuals with papillorenal syndrome and was absent from large population studies. In most PAX2 transcripts, this duplication is located in the 3' splice region of intron 1. While computational tools do not predict a splicing impact, this information is not predictive enough to rule out pathogenicity. It should also be noted this variant falls within the coding region of at least one PAX2 transcript (ENST00000554172.1: c.44_48dup (p.Ser17ValfsX10)) that is expressed in kidney tissue (GTEx, https://www.gtexportal.org/home/). On the ENST00000554172.1 transcript, the duplication is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 17 and leads to a premature termination codon 10 amino acids downstream. While loss of function of the PAX2 gene is an established disease mechanism for autosomal dominant papillorenal syndrome, at this time there is insufficient evidence to determine if ENST00000554172.1 is a biologically relevant transcript. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2.
Labcorp Genetics (formerly Invitae), Labcorp RCV002560205 SCV002991283 uncertain significance Renal coloboma syndrome; Focal segmental glomerulosclerosis 7 2022-09-12 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. ClinVar contains an entry for this variant (Variation ID: 930167). This variant has not been reported in the literature in individuals affected with PAX2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 1 of the PAX2 gene. It does not directly change the encoded amino acid sequence of the PAX2 protein.

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