ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.2171_2172del (p.Asn723_Phe724insTer)

dbSNP: rs1556205980
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657811 SCV000779566 likely pathogenic not provided 2018-05-22 criteria provided, single submitter clinical testing The c.2171_2172delTT variant in the PHEX gene has been reported previously in association with X-linked Hypophosphatemic Rickets (Cho et al., 2005). The deletion creates a premature Stop codon at position Phenylalanine 724, denoted p.Phe724Term. This variant is predicted to cause loss of normal protein function through protein truncation as the last 26 amino acids are lost. The c.2171_2172delTT variant is not observed in large population cohorts (Lek et al., 2016). This variant is likely pathogenic.
Invitae RCV000657811 SCV004299533 pathogenic not provided 2022-11-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PHEX protein in which other variant(s) (p.Arg747*) have been determined to be pathogenic (PMID: 9199930, 9768674). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 546044). This premature translational stop signal has been observed in individual(s) with hypophosphatemia (PMID: 16055933, 32253725). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe724*) in the PHEX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the PHEX protein.

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