Submissions for variant NM_000444.6(PHEX):c.2104C>T (p.Arg702Ter)

dbSNP: rs886041226

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000315034	SCV000329464	pathogenic	not provided	2021-12-23	criteria provided, single submitter	clinical testing	Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 48 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Reported in multiple unrelated individuals with hypophosphatemic rickets (Rowe et al., 1997; Holm et al., 2001; Zivicnjak et al., 2011; Morey et al., 2011; Cheon et al., 2014; Zhang et al., 2015; Acar et al., 2018; Lin et al., 2020; Thiele et al., 2020); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25894638, 16636593, 9768674, 32253725, 24926462, 26377240, 11502829, 23079138, 19219621, 21994957, 21902834, 29505567, 30682568, 33107440, 34434907, 34141703, 9097956)
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München	RCV000505471	SCV000599661	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2017-06-12	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000315034	SCV001144926	pathogenic	not provided	2018-10-04	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data.
Invitae	RCV000315034	SCV001214302	pathogenic	not provided	2023-09-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg702*) in the PHEX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the PHEX protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypophosphatemic rickets (PMID: 9097956, 9768674, 21902834, 23079138, 29505567). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 279872). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003401222	SCV004119741	pathogenic	PHEX-related condition	2022-11-22	criteria provided, single submitter	clinical testing	The PHEX c.2104C>T variant is predicted to result in premature protein termination (p.Arg702*). This variant was reported to be pathogenic for X-linked hypophosphataemic rickets (see examples: Rowe et al 1997. PubMed ID: 9097956; Figure 3A, Zhang et al 2019. PubMed ID: 30682568; Table S1, Park et al 2021. PubMed ID: 34434907). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in PHEX are expected to be pathogenic. This variant is interpreted as pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003483600	SCV004231798	benign	not specified	2024-01-12	criteria provided, single submitter	research