Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002026081 | SCV002304336 | likely pathogenic | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has been observed in individual(s) with PHEX-related conditions and/or X-linked hypophosphatemia (PMID: 30682568; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 16 of the PHEX gene. It does not directly change the encoded amino acid sequence of the PHEX protein. It affects a nucleotide within the consensus splice site of the intron. |
| Victorian Clinical Genetics Services, |
RCV004785457 | SCV005398353 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2024-10-08 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with hypophosphataemic rickets, X-linked dominant (MIM#307800). (I) 0110 - This gene is associated with X-linked dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Intrafamilial variability has been reported (PMID:22319799). (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another splice site variant comparable to the one identified in this case has limited previous evidence for pathogenicity. c.1700+5G>C has been reported in two individuals from one family with X-linked hypophosphataemia (PMID:36060934). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been reported in ClinVar once as likely pathogenic, and in the literature in an individual with X-linked hypophosphataemia (PMID: 30682568). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |