ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.920+6C>T

gnomAD frequency: 0.00013  dbSNP: rs730881964
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160980 SCV000211690 benign not specified 2014-08-27 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.
Invitae RCV000205864 SCV000261353 likely benign Peutz-Jeghers syndrome 2021-12-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000582092 SCV000691561 likely benign Hereditary cancer-predisposing syndrome 2016-06-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160980 SCV000918285 benign not specified 2017-09-07 criteria provided, single submitter clinical testing Variant summary: c.1008+8A>G in CHEK2 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of gnomAD at frequency of 0.000129 (4/ 30932 chrs tested), exclusively in individuals of European (NFE) descent (0.00026; 4/14982 chrs tested). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.0000063, suggesting that it is likely to be a common polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but is cited as Benign/Likely Benign by reputable database/clinical laboratory. Taking together, the variant was classified as Benign.
Illumina Laboratory Services,Illumina RCV000205864 SCV001285138 uncertain significance 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab RCV000205864 SCV002057300 likely benign Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000160980 SCV002071378 likely benign not specified 2021-03-10 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001356709 SCV002585692 likely benign not provided 2022-09-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356709 SCV001551950 likely benign not provided no assertion criteria provided clinical testing The STK11 c.920+6C>T variant was not identified in the literature, nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs730881964) as "With Likely benign allele" and in ClinVar (classified as benign by GeneDx; and as likely benign by Invitae and Color). The variant was identified in control databases in 4 of 30932 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 4 of 14982 chromosomes (freq: 0.0003), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The c.920+6C>T variant is located in the 5' splice region but does not affect the invariant +1 and +2 positions, although positions +3 to +6 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. However, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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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