Description
The CHEK2 p.Glu394Lys variant was not identified in the literature nor was it identified in the MutDB, or Zhejiang Colon Cancer Database. The variant was also identified in the following databases: dbSNP (ID: rs587780169) “With Uncertain significance allele”, ClinVar (classified uncertain significance by GeneDx, Ambry Genetics and Invitae), Clinvitae (3x), Cosmic (2x in a malignant melanoma and lymphoid neoplasm), and in control databases in 5 of 245908 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). Observations by population include European Non-Finnish in 3 of 111386 chromosomes (freq: 0.00003), and Ashkenazi Jewish in 2 of 9846 chromosomes (freq: 0.0002); it was not observed in the African, “Other”, Latino, East Asian, European Finnish, and South Asian populations. The p.Glu394 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the Lys variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 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. This variant is classified as a variant of uncertain significance.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
