Submissions for variant NM_000455.5(STK11):c.375-7G>A

gnomAD frequency: 0.00005  dbSNP: rs587781176

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000128292	SCV000171884	benign	not specified	2014-03-20	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.
Invitae	RCV000195449	SCV000253252	likely benign	Peutz-Jeghers syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Counsyl	RCV000195449	SCV000489016	likely benign	Peutz-Jeghers syndrome	2016-08-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000580100	SCV000686642	likely benign	Hereditary cancer-predisposing syndrome	2016-05-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586954	SCV000696717	likely benign	not provided	2017-02-02	criteria provided, single submitter	clinical testing	Variant summary: The STK11 c.375-7G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/29158 control chromosomes (1 homozygote) at a frequency of 0.0001372, which is approximately 22 times the estimated maximal expected allele frequency of a pathogenic STK11 variant (0.0000063), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likley benign. The variant was reported in one publication in an endometrial cancer patient, without strong evidence for causality (Ring_2016). While the small number of individuals in ExAC with this variant does not allow for the conclusive classification of benign, this variant has been classified as Likely Benign.
PreventionGenetics, part of Exact Sciences	RCV000586954	SCV000806077	likely benign	not provided	2018-01-17	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586954	SCV000889857	benign	not provided	2022-10-27	criteria provided, single submitter	clinical testing
Mendelics	RCV000195449	SCV001140936	likely benign	Peutz-Jeghers syndrome	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586954	SCV001151576	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	STK11: BP4, BS1
Genome-Nilou Lab	RCV000195449	SCV002057404	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580100	SCV002531688	likely benign	Hereditary cancer-predisposing syndrome	2021-07-05	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000195449	SCV004017990	uncertain significance	Peutz-Jeghers syndrome	2023-04-14	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.