Submissions for variant NM_000455.5(STK11):c.618G>A (p.Ala206=)

gnomAD frequency: 0.00018  dbSNP: rs370976710

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131380	SCV000186356	likely benign	Hereditary cancer-predisposing syndrome	2019-01-22	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.
GeneDx	RCV001704058	SCV000279180	likely benign	not provided	2019-10-22	criteria provided, single submitter	clinical testing
Invitae	RCV000477653	SCV000541168	benign	Peutz-Jeghers syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001704058	SCV000602234	benign	not provided	2020-12-18	criteria provided, single submitter	clinical testing
Counsyl	RCV000477653	SCV000784930	likely benign	Peutz-Jeghers syndrome	2017-02-06	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131380	SCV000910789	likely benign	Hereditary cancer-predisposing syndrome	2015-11-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000477653	SCV001284040	uncertain significance	Peutz-Jeghers syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798450	SCV002042773	likely benign	Breast and/or ovarian cancer	2020-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000477653	SCV002057272	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000131380	SCV002531718	benign	Hereditary cancer-predisposing syndrome	2020-10-08	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002267880	SCV002552019	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000477653	SCV004017995	benign	Peutz-Jeghers syndrome	2023-04-14	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000131380	SCV004227993	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-01	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000477653	SCV004816390	likely benign	Peutz-Jeghers syndrome	2023-12-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357059	SCV001552392	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Ala206= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs370976710) as "With Likely benign, other allele" and ClinVar (classified as benign by Invitae; as likely benign by Ambry Genetics, GeneDx and Counsyl; and as uncertain significance by one clinical laboratory). The variant was identified in 48 of 240844 chromosomes at a frequency of 0.0002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 1 of 107104 chromosomes (freq: 0.000009), Ashkenazi Jewish in 24 of 9264 chromosomes (freq: 0.003), and Finnish in 23 of 22390 chromosomes (freq: 0.001); it was not observed in the African, Other, Latino, East Asian, or South Asian populations. The p.Ala206= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site, although 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genetic Services Laboratory, University of Chicago	RCV002267880	SCV003840087	likely benign	not specified	2022-12-14	no assertion criteria provided	clinical testing