Submissions for variant NM_000455.5(STK11):c.1109-5C>T

gnomAD frequency: 0.00004  dbSNP: rs587782020

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130449	SCV000185313	likely benign	Hereditary cancer-predisposing syndrome	2018-06-11	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.
Invitae	RCV000200085	SCV000252699	benign	Peutz-Jeghers syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000200085	SCV000488597	uncertain significance	Peutz-Jeghers syndrome	2016-05-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000130449	SCV000903034	benign	Hereditary cancer-predisposing syndrome	2016-07-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780768	SCV000918294	benign	not specified	2018-07-13	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.1109-5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, however 5/5 computational tools predict no significant impact on normal splicing. These predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00017 in 267348 control chromosomes (gnomAD). The observed variant frequency is approximately 28-fold of the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Peutz-Jeghers Syndrome phenotype (6.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1109-5C>T in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2x likely benign/benign, 1x VUS). Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000780768	SCV001469910	benign	not specified	2020-05-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001711399	SCV001944007	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000200085	SCV002057310	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130449	SCV002531638	benign	Hereditary cancer-predisposing syndrome	2022-01-09	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000200085	SCV004017985	likely benign	Peutz-Jeghers syndrome	2023-04-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
PreventionGenetics, part of Exact Sciences	RCV003935221	SCV004759235	likely benign	STK11-related disorder	2019-10-23	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).