Submissions for variant NM_000455.5(STK11):c.651G>A (p.Pro217=)

gnomAD frequency: 0.00004  dbSNP: rs368348370

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163335	SCV000213869	likely benign	Hereditary cancer-predisposing syndrome	2014-12-18	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	RCV000199595	SCV000253260	likely benign	Peutz-Jeghers syndrome	2024-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000434357	SCV000514797	benign	not specified	2015-06-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health	RCV000163335	SCV000537500	likely benign	Hereditary cancer-predisposing syndrome	2015-11-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000434357	SCV000918280	benign	not specified	2017-10-20	criteria provided, single submitter	clinical testing	Variant summary: The STK11 c.651G>A (p.Pro217Pro) variant involves the alteration of a non-conserved nucleotide located in the protein kinase domain (IPR000719) (InterPro), resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESEfinder predicts that this variant may affect binding of ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 10/263042 control chromosomes at a frequency of 0.000038 (gnomAD), which is approximately 6 times the estimated maximal expected allele frequency of a pathogenic STK11 variant (0.0000063), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. One internal sample carrying this variant also carried another likely pathogenic variant ATM c.1A>C. Taken together, this variant is classified as benign.
Genome-Nilou Lab	RCV000199595	SCV002057422	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163335	SCV002531721	benign	Hereditary cancer-predisposing syndrome	2021-02-08	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000434357	SCV002773988	benign	not specified	2021-06-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000434357	SCV004026947	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000199595	SCV004818880	likely benign	Peutz-Jeghers syndrome	2024-02-05	criteria provided, single submitter	clinical testing