ClinVar

Description

The STK11 p.Pro315= variant was identified in 2 of 144 proband chromosomes (frequency: 0.01) from Spanish and Australian individuals or families with Lynch syndrome or PJS (Peutz–Jeghers syndrome (Vargas-Parra_2017_28577310, Scott_2002_12372054 ). The variant was also identified in dbSNP (ID: rs376329042) “With Likely benign allele”, ClinVar (classified benign by Invitae, GeneDx, and Quest Diagnostics Nichols Institute San Juan Capistrano, and likely benign by Ambry Genetics), Clinvitae (3x), Cosmic (1x in a carcinoma of the large intestine), Zhejiang Colon Cancer Database (8x), and in control databases in 150 of 218304 chromosomes at a frequency of 0.0007 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3 of 19118 chromosomes (freq: 0.0002), Other in 3 of 5448 chromosomes (freq: 0.0006), Latino in 10 of 28572 chromosomes (freq: 0.0004), European Non-Finnish in 66 of 95490 chromosomes (freq: 0.0007), Ashkenazi Jewish in 48 of 8990 chromosomes (freq: 0.005), European Finnish in 2 of 20554 chromosomes (freq: 0.0001), and South Asian in 18 of 25328 chromosomes (freq: 0.0007) while not observed in the East Asian population. The variant was not identified in MutDB, LOVD 3.0, and Insight Hereditary Tumors Database The p.Pro315= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. 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.