Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002308616 | SCV002600575 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2022-10-19 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the duplication of exons 18-20 in the PHEX gene. A presumed nomenclature of c.(1768+1_1769-1)_(2070+1_2071-1)dup has been designated for the purposes of this classification. It has been assumed that this is a tandem duplication in direct orientation (Richardson_GIM_2018, Newman_AJHG_2015). Although exact breakpoints of this duplication are not known, it is expected to result in a frameshift in the PHEX gene, a known mechanism of disease. The variant was absent in 16120 control chromosomes (gnomAD, Structural Variants dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. Duplication of exons 18-20 has been reported in the literature in two individuals suspected of X-Linked Hypophosphatemic Rickets, however they ultimately did not receive a clinical diagnosis (e.g. Rush_2022). Therefore, this report does not provide unequivocal conclusions about association of the variant with X-Linked Hypophosphatemic Rickets. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |