ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.615G>A (p.Ala205=) (rs532889728)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000213016 SCV000211684 benign not specified 2014-06-09 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 RCV000160974 SCV000213651 likely benign Hereditary cancer-predisposing syndrome 2015-03-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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 RCV000229020 SCV000284870 likely benign Peutz-Jeghers syndrome 2020-12-06 criteria provided, single submitter clinical testing
Counsyl RCV000229020 SCV000488658 likely benign Peutz-Jeghers syndrome 2016-05-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV000160974 SCV000691530 likely benign Hereditary cancer-predisposing syndrome 2019-12-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759355 SCV000888641 likely benign not provided 2017-11-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000759355 SCV001151578 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000229020 SCV001284038 likely benign Peutz-Jeghers syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000213016 SCV001338171 likely benign not specified 2020-02-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000229020 SCV001553312 likely benign Peutz-Jeghers syndrome no assertion criteria provided clinical testing The STK11 p.Ala205= variant was identified in 1 of 14102 proband chromosomes (frequency: 0.00007) from individuals or families with breast cancer and was not identified in 22482 control chromosomes from healthy individuals (Momozawa, 2018). The variant was also identified in dbSNP (ID: rs532889728) as “With other allele”, ClinVar (classified as benign by GeneDx, as likely benign by Ambry Genetics and Counsyl, and as uncertain significance by Invitae and Color Genomics), LOVD 3.0 (classified as uncertain significance). The variant was identified in control databases in 10 of 238092 chromosomes at a frequency of 0.000042 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 2 of 30902 chromosomes (freq: 0.000065), European Non-Finnish in 6 of 105662 chromosomes (freq: 0.000057), East Asian in 2 of 16486 chromosomes (freq: 0.0001), while the variant was not observed in the African, Other, Ashkenazi Jewish, European Finnish, and South Asian populations. The variant has been observed in our laboratory in a patient with pancreatic cancer with an alternate molecular basis for disease (ATM c.1A>G). In a study of STK11 variants this variant was observed to demonstrate IHC stain intensity comparable to wild type (Pelak, 2013). The p.Ala205= 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. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; however, this information is not predictive enough to assume pathogenicity. 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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