Total submissions: 2
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, |
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. |