Submissions for variant NM_000455.5(STK11):c.1108+3G>A

gnomAD frequency: 0.00002  dbSNP: rs755746417

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000230024	SCV000284842	likely benign	Peutz-Jeghers syndrome	2024-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001697298	SCV000532358	likely benign	not provided	2019-10-16	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000445130	SCV000602206	likely benign	not specified	2017-07-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000561129	SCV000664353	uncertain significance	Hereditary cancer-predisposing syndrome	2021-07-16	criteria provided, single submitter	clinical testing	The c.1108+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 8 in the STK11 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000561129	SCV000691471	likely benign	Hereditary cancer-predisposing syndrome	2017-08-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000445130	SCV000918288	uncertain significance	not specified	2021-12-02	criteria provided, single submitter	clinical testing	Variant summary: STK11 c.1108+3G>A 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. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.1e-05 in 239710 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1108+3G>A in individuals affected with Peutz-Jeghers Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A co-occurrence with a pathogenic variant has been reported via internal testing (ATM c.6280G>T, p.Glu2094X). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=4) and as uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab	RCV000230024	SCV002057309	likely benign	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003491999	SCV004239714	uncertain significance	Breast and/or ovarian cancer	2022-12-08	criteria provided, single submitter	clinical testing