ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.-764G>A (rs587776674)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000230941 SCV000840498 uncertain significance PTEN hamartoma tumor syndrome 2018-04-06 reviewed by expert panel curation PTEN c.-764G>A (NC_000010.10:g.89623462G>A) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). PM2: Present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533).
GeneDx RCV000169801 SCV000222117 uncertain significance not provided 2018-07-12 criteria provided, single submitter clinical testing This variant is denoted PTEN c.-765G>A, and describes a nucleotide substitution 765 base pairs upstream of the ATG translational start site in the PTEN promoter region. The surrounding sequence, with the base that is substituted in brackets, is CGAG[G/A]GAGA. This variant, also known as PTEN c.-764G>A using alternate numbering, has been reported in at least two individuals, one with breast cancer and another with a benign breast neoplasm and endometrial cancer (Zhou 2003, Teresi 2007). While a reporter assay found that this variant was associated with a 60% decrease in luciferase activity as compared to wild type, the luciferase mRNA levels were similar to wild type, which was interpreted as suggesting that transcription efficiency and mRNA stability are not compromised by this variant (Teresi 2007). Additionally, Fuxman Bass et al. (2015) demonstrated that this variant resulted in lost protein-DNA interaction and decreased expression by enhanced yeast one-hybrid assay. Based on currently available evidence, it is unclear whether PTEN c.-765G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000230941 SCV000284573 uncertain significance PTEN hamartoma tumor syndrome 2016-03-28 criteria provided, single submitter clinical testing
Counsyl RCV000008294 SCV000785100 uncertain significance Cowden syndrome 1 2017-04-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763685 SCV000894565 uncertain significance Macrocephaly/autism syndrome; Meningioma, familial; Malignant tumor of prostate; VACTERL association with hydrocephalus; Glioma susceptibility 2; PTEN hamartoma tumor syndrome; Cowden syndrome 1 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000008294 SCV000028501 pathogenic Cowden syndrome 1 2007-10-01 no assertion criteria provided literature only

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