PIK3CA encodes the catalytic subunit of Phosphatidylinositol 3-kinase (PIK3), which phosphorylates PIP2 to PIP3 and activates the signaling pathway. Monoallelic PIK3CA activating mutations are associated with overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (MONDO:0100283). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we only focus on hereditary breast cancer in this curation. Evidence curated in this gene-disease relationship includes case-control data.
Summary of Case-Control Data: 0 point This gene-disease relationship has been studied in at least 1 case-control study at the aggregate variant level. In 2021, a large case-control study [BCAC (PMID: 33471991) with more than 48 thousand cases and controls] did not identify a significant association of aggregate loss of function (LOF) variants in PI3KCA and breast cancer.
Overall Summary: In summary, given the lack of significant association in large breast cancer case-control studies to date, there is convincing evidence refuting the association between PI3KCA and autosomal dominant hereditary breast cancer. This gene-disease pair was originally evaluated as no known disease relationship by the Breast/Ovarian Cancer GCEP on 2/8//2017. This re-curation was approved by the ClinGen Hereditary Diseases GCEP on 6/9/2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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