Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000595534 | SCV000708173 | pathogenic | not provided | 2017-05-02 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193268 | SCV001361999 | likely pathogenic | Nephronophthisis 4 | 2019-03-05 | criteria provided, single submitter | clinical testing | Variant summary: NPHP4 c.189_192delTGAT (p.Phe63LeufsX16) 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. Truncations downstream of this position have been reported in several individuals affected with Nephronophthisis 4 in HGMD. The variant allele was found at a frequency of 4.2e-06 in 238746 control chromosomes (gnomAD). To our knowledge, no occurrence of c.189_192delTGAT in individuals affected with Nephronophthisis 4, and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Invitae | RCV003117367 | SCV003789288 | pathogenic | Nephronophthisis | 2022-07-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 501697). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Phe63Leufs*16) in the NPHP4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHP4 are known to be pathogenic (PMID: 12205563, 23559409). |