Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000269158 | SCV000330608 | pathogenic | not provided | 2017-01-25 | criteria provided, single submitter | clinical testing | The c.1587-1 G>A splice site variant in the PHEX gene destroys the canonical splice acceptor site in intron 14. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1587-1 G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Another pathogenic variant at this nucleotide (c.1587-1 G>C) has been observed at GeneDx and published as a pathogenic variant in a patient diagnosed with hypophosphatemic rickets (Beck-Nielsen et al., 2012). Although this pathogenic variant has not been previously reported to our knowledge, its presence is consistent with the diagnosis of X-linked hypophosphatemic rickets. |
Invitae | RCV000269158 | SCV001230528 | pathogenic | not provided | 2021-04-02 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in an individual affected with hypophosphatemic rickets (PMID: 22695891). ClinVar contains an entry for this variant (Variation ID: 280672). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 14 of the PHEX gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Genomic Research Center, |
RCV001169961 | SCV001251670 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2020-05-03 | criteria provided, single submitter | clinical testing |