ClinVar

Description

The STK11 c.464+9G>A variant was not identified in the literature. The variant was identified in dbSNP (ID: rs376313955) as "With other allele", in ClinVar (5x Benign by Invitae, GeneDx and three other submitters, 5x likely benign by Ambry Genetics and four other submitters), and in LOVD 3.0 (classified as likely benign). The variant was identified in control databases in 165 of 203546 chromosomes at a frequency of 0.0008, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 132 of 18030 chromosomes (freq: 0.007), Other in 4 of 5186 chromosomes (freq: 0.0008), Latino in 26 of 27178 chromosomes (freq: 0.001), European in 2 of 87470 chromosomes (freq: 0.00002) and East Asian in 1 of 13646 chromosomes (freq: 0.00007); it was not observed in the Ashkenazi Jewish, Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. However, this information is not predictive enough to assume pathogenicity. 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.