ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.609T>G (p.Asp203Glu)

dbSNP: rs587781563
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129584 SCV000184366 uncertain significance Hereditary cancer-predisposing syndrome 2013-10-29 criteria provided, single submitter clinical testing The p.D203E variant (also known as c.609T>G) is located in coding exon 4 of the CHEK2 gene. This alteration results from a T to G substitution at nucleotide position 609. The aspartic acid at codon 203 is replaced by glutamic acid, an amino acid with highly similar properties. No population frequency information could be foundin the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 8000 alleles tested) in our clinical cohort (includes this individual). Based on protein sequence alignment, this amino acid position is completely conserved in available vertebrate species. However, this alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.D203E remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781296 SCV000919215 uncertain significance not specified 2017-10-20 criteria provided, single submitter clinical testing Variant summary: The CHEK2 variant, c.609T>G (p.Asp203Glu) causes a missense change involving a non-conserved nucleotide and 3/4 in silico tools predict benign outcome (SNPSandGO not captured here due to low reliability index). However, no functional studies supporting these predictions were published at the time of evaluation. The variant is indicated to not be located in a known functional domain (via InterPro). The c.609T>G is absent from the control population datasets of ExAC and gnomAD (53922 and 212176 chromosomes tested, respectively). To our knowledge, the variant has not been reported in affected individuals via published reports, but is cited as VUS by a clinical diagnostic laboratoru. Taken together, the variant has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.