ClinVar

Description

Variant summary: STK11 c.863-5_863-3delCTC alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Four computational tools predict the variant weakens a 3 acceptor site. c.863-5_863-3delCTC has been reported in the literature in an individual that did not have any clinical characteristics of Peutz-Jeghers syndrome. RNAseq analysis of the patient blood sample revealed an abnormal transcript that lacks exon 7. However, this out-of-frame transcript was minorly expressed (only in 0.9%), implying that the variant causes an insignificant splicing abnormality (Dragos_2021). The variant was absent in 159362 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. Co-occurrence with a pathogenic variant has been observed via internal testing (BRCA2 c.100G>T, p.E34X). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=3) and as likely benign (n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.