ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.1167C>G (p.Ala389=) (rs547919101)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165173 SCV000215885 likely benign Hereditary cancer-predisposing syndrome 2014-10-13 criteria provided, single submitter clinical testing
GeneDx RCV000756724 SCV000568854 uncertain significance not provided 2016-05-16 criteria provided, single submitter clinical testing This variant is denoted STK11 c.1167C>G at the DNA level. Although this variant is silent at the coding level, preserving an Alanine at codon 389, it is predicted to cause the gain of a cryptic splice donor site 150bp upstream of the natural splice donor site for intron 9. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 c.1167C>G was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The nucleotide which is altered, a cytosine (C) at base 1167, is not conserved. Based on currently available evidence, it is unclear whether STK11 c.1167C>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000558075 SCV000629070 uncertain significance Peutz-Jeghers syndrome 2017-12-14 criteria provided, single submitter clinical testing This sequence change affects codon 389 of the STK11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the STK11 protein. This variant is present in population databases (rs547919101, ExAC 0.004%). This variant has not been reported in the literature in individuals with a STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 185703). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant has uncertain impact on STK11 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756724 SCV000884616 uncertain significance not provided 2018-06-19 criteria provided, single submitter clinical testing The STK11 c.1167C>G; p.Ala389Ala variant (rs547919101), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 185703). This variant is found in the general population with an overall allele frequency of 0.004% (9/237420 alleles) in the Genome Aggregation Database. This is a synonymous variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating or strengthening a novel cryptic donor splice site upstream of the canonical donor site. However, given the lack of clinical and functional data, the significance of the p.Ala389Ala variant is uncertain at this time.
Color RCV000165173 SCV000903948 likely benign Hereditary cancer-predisposing syndrome 2016-11-04 criteria provided, single submitter clinical testing

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