Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000443391 | SCV000517393 | likely pathogenic | not provided | 2018-12-07 | criteria provided, single submitter | clinical testing | The c.1568+2T>C variant in the PIK3R1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 12. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1568+2T>C variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1568+2T>C as a likely pathogenic variant. |
Center for Genomic Medicine, |
RCV003992292 | SCV004810332 | likely pathogenic | Agammaglobulinemia 7, autosomal recessive | 2024-04-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004022324 | SCV005006207 | uncertain significance | Inborn genetic diseases | 2024-01-30 | criteria provided, single submitter | clinical testing | The c.1568+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 11 of the PIK3R1 gene. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of PIK3R1 has not been established as a mechanism of disease. Based on data from gnomAD, the C allele has an overall frequency of <0.001% (1/233566) total alleles studied. The highest observed frequency was 0.001% (1/108410) of European (non-Finnish) alleles. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |