ClinVar

Description

The STK11 p.Ala347Ala variant was identified in 1 of 84 proband chromosomes (frequency: 0.01) from individuals or families with Peutz-Jaghers Syndrome (Amos 2004). The variant was identified in dbSNP (rs537906142) as “with likely benign, uncertain significance allele”, in ClinVar (interpreted as "benign" by Invitae and 2 others, "likely benign" by Ambry Genetics and "uncertain significance" by GeneDx). The variant was not identified in LOVD 3.0. The variant was identified in control databases in 27 of 241,514 chromosomes at a frequency of 0.0001 increasing the likelihood this could be a low frequency benign variant as this frequency is well above the known prevalence of Peutz-Jagher Syndrome (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 1 of 109,548 chromosomes (freq: 0.000009), Finnish in 1 of 21,340 chromosomes (freq: 0.00005), and South Asian in 25 of 30,278 chromosomes (freq: 0.0008). The variant was not observed in the African, Other, Latino, Ashkenazi Jewish, or East Asian populations. The p.Ala347= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicted the creation of a new splice site. 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.