Submissions for variant NM_000455.5(STK11):c.465-5C>T

gnomAD frequency: 0.00005  dbSNP: rs567202367

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130832	SCV000185729	likely benign	Hereditary cancer-predisposing syndrome	2018-09-28	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	RCV000199796	SCV000253257	likely benign	Peutz-Jeghers syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000199796	SCV000296921	uncertain significance	Peutz-Jeghers syndrome	2015-10-30	criteria provided, single submitter	clinical testing
Counsyl	RCV000199796	SCV000489545	likely benign	Peutz-Jeghers syndrome	2016-10-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000130832	SCV000686660	likely benign	Hereditary cancer-predisposing syndrome	2017-04-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001705929	SCV001837202	benign	not provided	2015-03-05	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001705929	SCV002046670	likely benign	not provided	2021-02-24	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000199796	SCV002057252	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130832	SCV002531704	likely benign	Hereditary cancer-predisposing syndrome	2022-03-01	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000199796	SCV004018023	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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003321514	SCV004026944	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492604	SCV004239727	uncertain significance	Breast and/or ovarian cancer	2023-05-17	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000199796	SCV004816707	likely benign	Peutz-Jeghers syndrome	2023-11-30	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355110	SCV001549897	uncertain significance	Carcinoma of colon		no assertion criteria provided	clinical testing	The STK11 c.465-5C>T variant was not identified in the literature nor was it identified in the LOVD 3.0, database. The variant was identified in dbSNP (ID: rs567202367) as “With other allele” and ClinVar (4x as likely benign and 1x as uncertain significance by Ambry Genetics, Invitae, Counsyl, Color and The Children Hospital of Philadelphia). The variant was identified in control databases in 1 of 30916 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 1 of 1622 chromosomes (freq: 0.0006), while the variant was not observed in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, European Finnish or South Asian populations. The c.465-5C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.