Submissions for variant NM_000455.5(STK11):c.621C>T (p.Asp207=)

gnomAD frequency: 0.00001  dbSNP: rs569380138

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163122	SCV000213634	likely benign	Hereditary cancer-predisposing syndrome	2014-10-22	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.
Invitae	RCV000230661	SCV000284871	likely benign	Peutz-Jeghers syndrome	2023-12-19	criteria provided, single submitter	clinical testing
Counsyl	RCV000230661	SCV000489440	likely benign	Peutz-Jeghers syndrome	2016-10-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163122	SCV000691531	likely benign	Hereditary cancer-predisposing syndrome	2017-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000759356	SCV000729206	likely benign	not provided	2021-09-13	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759356	SCV000888642	likely benign	not provided	2017-08-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000230661	SCV004017966	benign	Peutz-Jeghers syndrome	2023-04-13	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.
PreventionGenetics, part of Exact Sciences	RCV003982911	SCV004800597	likely benign	STK11-related disorder	2024-02-07	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).
All of Us Research Program, National Institutes of Health	RCV000230661	SCV004816393	likely benign	Peutz-Jeghers syndrome	2023-06-08	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356654	SCV001551884	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Asp207= variant was not identified in the literature nor was it identified in the LOVD 3.0, Zhejiang Colon Cancer Database, Insight Hereditary Tumors Database, databases. The variant was identified in dbSNP (ID: rs569380138) as With Likely benign allele, ClinVar (classified as likely benign by Ambry Genetics, Invitae, Counsyl), Clinvitae (classified as likely benign by ClinVar, Invitae), databases. The variant was identified in control databases in 3 of 210004 chromosomes at a frequency of 0.000014 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include Latino in 1 of 30480 chromosomes (freq: 0.000033), EuropeanNon-Finnish in 1 of 92130 chromosomes (freq: 0.000011), EastAsian in 1 of 15104 chromosomes (freq: 0.000066), while the variant was not observed in the African, Other, AshkenaziJewish, EuropeanFinnish, and SouthAsian populations. The p.Asp207= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign.