Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000819926 | SCV000960613 | uncertain significance | Immunodeficiency 14 | 2019-04-20 | criteria provided, single submitter | clinical testing | This sequence change affects codon 999 of the PIK3CD mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PIK3CD protein. This variant also falls at the last nucleotide of exon 23 of the PIK3CD coding sequence, which is part of the consensus splice site for this exon. 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. Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with PIK3CD-related disease. This variant is not present in population databases (ExAC no frequency). |
| Gene |
RCV001776039 | SCV002013639 | uncertain significance | not provided | 2019-09-06 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |
| Hudson |
RCV002245690 | SCV002515852 | uncertain significance | Immunodeficiency 14b, autosomal recessive | 2021-08-27 | criteria provided, single submitter | research | ACMG codes: PM2, PP3 |