Submissions for variant NM_000455.5(STK11):c.264C>A (p.Ile88=)

gnomAD frequency: 0.02303  dbSNP: rs56354945

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078912	SCV000110772	benign	not specified	2013-05-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000129391	SCV000184157	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	RCV000078912	SCV000304387	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000406309	SCV000410734	benign	Peutz-Jeghers syndrome	2018-01-13	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	RCV000406309	SCV000554137	benign	Peutz-Jeghers syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129391	SCV000686626	benign	Hereditary cancer-predisposing syndrome	2015-04-08	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001536943	SCV001156742	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001536943	SCV001753760	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000406309	SCV002057396	benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000129391	SCV002531678	benign	Hereditary cancer-predisposing syndrome	2020-10-20	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000078912	SCV002551947	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149766	SCV003838122	benign	Breast and/or ovarian cancer	2021-07-07	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000406309	SCV004015560	benign	Peutz-Jeghers syndrome	2023-07-07	criteria provided, single submitter	clinical testing
True Health Diagnostics	RCV000129391	SCV000788217	likely benign	Hereditary cancer-predisposing syndrome	2018-01-03	no assertion criteria provided	clinical testing
Faculté Pluridciplinaire Nador, Université Mohamed Premier	RCV001250944	SCV001250927	likely benign	Squamous cell lung carcinoma	2020-05-05	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357260	SCV001552679	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The STK11 p.Ile88= variant was not identified in the literature nor was it identified in the MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, or Insight Hereditary Tumors Database. The variant was identified in the following databases: dbSNP (ID: rs56354945) as “With other allele”, ClinVar (as likely benign by Illumina and benign by Emory Genetics, Ambry Genetics, PreventionGenetics, and Invitae), Clinvitae (4x), and Cosmic. The variant was identified in control databases in 1969 of 264616 chromosomes (67 homozygous) at a frequency of 0.007441 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Observations by population include African in 1688 (66 homozygous) of 22648 chromosomes (freq: 0.07453), Other in 26 of 6226 chromosomes (freq: 0.004176), Latino in 175 (1 homozygous) of 33114 chromosomes (freq: 0.005285), European (Non-Finnish) in 76 of 120564 chromosomes (freq: 0.00063), and South Asian in 4 of 29712 chromosomes (freq: 0.000135); the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish) populations. The p.Ile88= 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	RCV000078912	SCV001807299	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000078912	SCV001917838	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078912	SCV001953503	benign	not specified		no assertion criteria provided	clinical testing