Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000807422 | SCV000947473 | uncertain significance | Immunodeficiency 14 | 2022-01-02 | criteria provided, single submitter | clinical testing | This sequence change affects codon 414 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 9, 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. 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: 651966). This variant has not been reported in the literature in individuals affected with PIK3CD-related conditions. This variant is present in population databases (rs758253493, gnomAD 0.008%). |
Gene |
RCV001552565 | SCV001773271 | uncertain significance | not provided | 2019-11-20 | 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. |
Fulgent Genetics, |
RCV002501090 | SCV002814814 | uncertain significance | Combined immunodeficiency with faciooculoskeletal anomalies; Immunodeficiency 14; Immunodeficiency 14b, autosomal recessive | 2022-04-28 | criteria provided, single submitter | clinical testing |