ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.2071-1G>A

dbSNP: rs886041374
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000392446 SCV000329889 pathogenic not provided 2021-02-23 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25525159, 12414858, 30682568)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000505481 SCV000599690 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2013-11-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000392446 SCV001579963 pathogenic not provided 2020-01-10 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 20 of the PHEX gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been observed in individual(s) affected with hypophosphatemic rickets (PMID: 12414858, Invitae). ClinVar contains an entry for this variant (Variation ID: 280087). 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.
Illumina Laboratory Services, Illumina RCV000505481 SCV004101285 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2023-08-21 criteria provided, single submitter clinical testing The PHEX c.2071-1G>A variant results in a substitution at the consensus splice acceptor site, which may result in splicing defects. This variant has been identified in one individual with a phenotype consistent with X-linked hypophosphatemia (PMID: 12414858;30682568).This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. This variant was identified in a de novo state. Based on the available evidence, the c.2071-1G>A variant is classified as pathogenic for X-linked hypophosphatemia.

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