ClinVar Miner

Submissions for variant NM_006218.4(PIK3CA):c.2040T>C (p.Val680=)

gnomAD frequency: 0.00004  dbSNP: rs201402676
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Brain Malformations Variant Curation Expert Panel RCV001725187 SCV001960886 likely benign Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes 2022-02-11 reviewed by expert panel curation The NM_006218.4(PIK3CA): c.2040T>C (p.Val680=) variant is a synonymous (silent) variant that occurs at a nucleotide that is not conserved according to a PhyloP <0.1 (BP7). The results from in silico splicing predictors MaxEntScan, spliceAI and varSEAK support that this variant does not affect splicing (BP4). In summary, this variant meets the criteria to be classified as Likely benign for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: BP4, BP7; -2 points (VCEP specifications version 1; Approved: 1/31/2021)
Invitae RCV000535432 SCV000626812 likely benign Cowden syndrome 2023-11-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002420353 SCV002719749 likely benign Inborn genetic diseases 2022-03-16 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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