ClinVar Miner

Submissions for variant NM_001126049.2(KLLN):c.-1007C>T

dbSNP: rs587780001
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV001078168 SCV001244239 likely benign PTEN hamartoma tumor syndrome 2019-11-22 reviewed by expert panel curation PTEN c.-975G>A (NC_000010.10:g.89623251G>A) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). BS1: Allele frequency of 0.00127 (0.127%, 11/8660 alleles) in the African subpopulation of the gnomAD cohort. (PMID 27535533) BS2_P: Meets criteria for BS2 (observed in the homozygous state in at least one healthy or PHTS-unaffected individual) but BS1 is also applied. (internal laboratory contributor ClinVar Organization ID: 61756)
GeneDx RCV000587663 SCV000149488 benign not provided 2017-12-06 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25669429)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587663 SCV000696554 benign not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The PTEN c.-975G>A (also known as c.-976G>A) variant involves the alteration of a non-conserved nucleotide located in the promoter region of PTEN. One in silico tool predicts a benign outcome for this variant. This variant was found in 20/30846 control chromosomes (gnomAD) at a frequency of 0.0006484, which is approximately 104 times the estimated maximal expected allele frequency of a pathogenic PTEN variant (0.0000063), suggesting this variant is likely a benign polymorphism. A publication, Nizialek_2015, cites the variant to have been found in their cohort, however, it is unclear as to whether the variant was found in affected individuals or controls. Although the authors do report another variant at this position, c.-976G>C that segregated with CS in the family and was observed to have promoter methylation, although methylation is commonly associated with C residues. A clinical diagnostic laboratory cites the variant as "uncertain significance." In addition, an internal LCA sample reports the variant to co-occur with a likely pathogenic TP53 variant, c.375+2T>C. Therefore, the variant of interest has been classified as Benign.
Genetic Services Laboratory,University of Chicago RCV001818272 SCV002071955 uncertain significance not specified 2019-04-25 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV002256044 SCV002528279 benign Hereditary cancer-predisposing syndrome 2020-09-29 criteria provided, single submitter curation

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