Submissions for variant NM_000455.4(STK11):c.375-7G>A (rs587781176)

Total submissions: 8

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	2017-12-21	criteria provided, single submitter	clinical testing
Counsyl	RCV000195449	SCV000489016	likely benign	Peutz-Jeghers syndrome	2016-08-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000128292	SCV000602222	likely benign	not specified	2016-12-17	criteria provided, single submitter	clinical testing
Color	RCV000580100	SCV000686642	likely benign	Hereditary cancer-predisposing syndrome	2016-05-24	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	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,PreventionGenetics	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	2018-08-09	criteria provided, single submitter	clinical testing