ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1194G>A (p.Ala398=) (rs184271025)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080617 SCV000166350 benign Peutz-Jeghers syndrome 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000213034 SCV000171896 benign not specified 2014-01-30 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.
Ambry Genetics RCV000128304 SCV000212677 likely benign Hereditary cancer-predisposing syndrome 2014-07-04 criteria provided, single submitter clinical testing In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign
Color Health, Inc RCV000128304 SCV000686603 likely benign Hereditary cancer-predisposing syndrome 2015-04-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588156 SCV000696706 benign not provided 2016-07-01 criteria provided, single submitter clinical testing Variant summary: The STK11 c.1194G>A (p.Ala398Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant, and 5/5 splicing algorithms predict no significant change to normal splicing. This variant was found in 22/67290 control chromosomes at a frequency of 0.0003269, which is approximately 52 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 Benign/Likely Benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together and based on the synonymous nature of this variant and the high allele frequency in the general population, this variant is classified as Benign.
PreventionGenetics,PreventionGenetics RCV000588156 SCV000806070 likely benign not provided 2017-06-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588156 SCV000888638 benign not provided 2018-05-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001080617 SCV001287492 likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357670 SCV001553204 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The STK11 p.Ala398= variant was not identified in the literature nor was it identified in the Cosmic, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database or Insight Hereditary Tumors Database. The variant was identified in the following databases: dbSNP (ID: rs184271025) as “With Likely benign allele” and ClinVar (2x as benign by GeneDx, Integrated Genetics and 3x as likely benign by Invitae, Ambry Genetics and Color Genomics). The variant was identified in control databases in 74 of 255414 chromosomes at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the “Other” population in 4 of 6024 chromosomes (freq: 0.00066), Latino in 18 of 33034 chromosomes (freq: 0.0005), European Non-Finnish in 45 of 115132 chromosomes (freq: 0.0004), and Finnish in 7 of 23466 chromosomes (freq: 0.0003); it was not observed in the African, Ashkenazi Jewish, East Asian or South Asian populations. The p.Ala398= 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.

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