Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705764 | SCV000834778 | uncertain significance | Familial cancer of breast | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 296 of the CHEK2 protein (p.Asp296Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 581826). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown this missense change is associated with skipping of exon 8, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Color Diagnostics, |
RCV001525428 | SCV001735524 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-29 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 296 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/217246 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV001525428 | SCV002685311 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-17 | criteria provided, single submitter | clinical testing | The p.D296G variant (also known as c.887A>G), located in coding exon 7 of the CHEK2 gene, results from an A to G substitution at nucleotide position 887. The aspartic acid at codon 296 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV000705764 | SCV004217577 | uncertain significance | Familial cancer of breast | 2023-09-03 | criteria provided, single submitter | clinical testing |