Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413865 | SCV000490716 | likely pathogenic | not provided | 2016-06-10 | criteria provided, single submitter | clinical testing | The c.2070+5 variant has not been published as a pathogenic variant, nor has it been reported as abenign variant to our knowledge. It was not observed in approximately 6,500 individuals of Europeanand African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not acommon benign variant in these populations. Several in-silico splice prediction models predict thatc.2070+5 G>C destroys the natural splice donor site for exon 20, which may lead to abnormal genesplicing. However, in the absence of RNA/functional studies, the actual effect of this sequence changeis unknown. Therefore, this variant is likely pathogenic; however, the possibility thatit is benign cannot be excluded. |
Invitae | RCV000413865 | SCV002180756 | uncertain significance | not provided | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 20 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. ClinVar contains an entry for this variant (Variation ID: 372463). This variant has been observed in individual(s) with PHEX-related conditions (Invitae). This variant is not present in population databases (ExAC no frequency). |