Submissions for variant NM_000455.5(STK11):c.816C>T (p.Tyr272=)

gnomAD frequency: 0.02603  dbSNP: rs9282859

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129587	SCV000184370	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
PreventionGenetics, part of Exact Sciences	RCV000241793	SCV000304394	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000333429	SCV000410744	benign	Peutz-Jeghers syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000333429	SCV000554120	benign	Peutz-Jeghers syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129587	SCV000686691	benign	Hereditary cancer-predisposing syndrome	2015-04-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000241793	SCV000884612	benign	not specified	2018-07-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001580067	SCV001895628	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000333429	SCV002057437	benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000241793	SCV002552025	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149892	SCV003838175	benign	Breast and/or ovarian cancer	2021-10-05	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000333429	SCV004015559	benign	Peutz-Jeghers syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000241793	SCV000692050	benign	not specified		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000129587	SCV000788220	likely benign	Hereditary cancer-predisposing syndrome	2018-02-20	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355314	SCV001550171	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Tyr272Tyr variant was not identified in the literature nor was it identified in the MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, and Insight Hereditary Tumors Database databases. The variant was identified in dbSNP (ID: rs9282859) as “Other”, ClinVar (classified benign by Ambry Genetics and Prevention Genetics, and likely benign by Illumina), and in Cosmic (3X all in lung carcinomas). The variant was also identified in control databases in 2204 (84 homozygous) of 273338 chromosomes at a frequency of 0.008 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017), identified in the following populations at a frequency greater than 1%: African in 1993 of 23530 chromosomes (freq: 0.085). The p.Tyr272Tyr 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 this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580067	SCV001809549	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000241793	SCV001923010	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000241793	SCV001958876	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000241793	SCV002036443	benign	not specified		no assertion criteria provided	clinical testing