ClinVar

Description

The KNL1 p.Leu2104Trp variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs115973566) and was also found in control databases in 18 of 270658 chromosomes at a frequency of 0.000067 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 16 of 23962 chromosomes (freq: 0.000668) and Latino in 2 of 32316 chromosomes (freq: 0.000062), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Other, 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. The p.Leu2104 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.