ClinVar Miner

Submissions for variant NM_000455.4(STK11):c.464+5G>A (rs587781681)

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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 RCV000129842 SCV000184659 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000480137 SCV000566638 uncertain significance not specified 2017-05-30 criteria provided, single submitter clinical testing This variant is denoted STK11 c.464+5G>A or IVS3+5G>A and consists of a G>A nucleotide substitution at the +5 position of intron 3 of the STK11 gene. Multiple in silico models predict this variant to damage or destroy the nearby natural splice donor site and to possibly cause abnormal gene splicing. 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.464+5G>A was not observed in approximately 6,500 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 guanine (G) nucleotide that is altered is conserved across species. Based on currently available evidence, it is unclear whether STK11 c.464+5G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000537602 SCV000629117 uncertain significance Peutz-Jeghers syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the STK11 gene. It does not directly change the encoded amino acid sequence of the STK11 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs587781681, ExAC 0.005%). This variant has not been reported in the literature in individuals with STK11-related disease. ClinVar contains an entry for this variant (Variation ID: 141354). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000129842 SCV000686655 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765430 SCV000896714 uncertain significance Carcinoma of pancreas; Peutz-Jeghers syndrome; Malignant tumor of testis 2018-10-31 criteria provided, single submitter clinical testing

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