Submissions for variant NM_000455.5(STK11):c.-2G>T

gnomAD frequency: 0.00007  dbSNP: rs774072752

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000288357	SCV000410732	benign	Peutz-Jeghers syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000436151	SCV000514789	benign	not specified	2015-06-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000492081	SCV000580942	likely benign	Hereditary cancer-predisposing syndrome	2020-09-04	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000436151	SCV000602220	benign	not specified	2021-08-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586834	SCV000696714	benign	not provided	2016-06-27	criteria provided, single submitter	clinical testing	Variant summary: The STK11 c.-2G>T variant is located in the 5'UTR involving a conserved nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing and alterations to ESE binding, although these predictions have yet to be functionally assesed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 6/24392 (1/4065), predominantly in the Latino cohort, 6/916 (1/152), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic STK11 variant of 1/158730. Therefore, suggesting the variant of interest is a common polymorphism found in population(s) of Latino origin. The variant of interest was has not been, to our knowledge, reported in affected individuals via publications and/or reputable databases/clinical laboratories. However, an internal LCA specimen reports the variant to co-occur with another potentially pathogenic MLH1 variant, c.1731+1G>T (scored "likely pathogenic"). Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
PreventionGenetics, part of Exact Sciences	RCV000586834	SCV000806066	likely benign	not provided	2017-07-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000492081	SCV000903058	likely benign	Hereditary cancer-predisposing syndrome	2015-04-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000288357	SCV002057223	benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000436151	SCV002072420	uncertain significance	not specified	2019-07-01	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000288357	SCV004818830	likely benign	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing