Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000563058 | SCV000664777 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-05-04 | criteria provided, single submitter | clinical testing | The p.R2928K variant (also known as c.8783G>A), located in coding exon 59 of the ATM gene, results from a G to A substitution at nucleotide position 8783. The arginine at codon 2928 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000824591 | SCV000965494 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-03-27 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 480876). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 2928 of the ATM protein (p.Arg2928Lys). |
Color Diagnostics, |
RCV000563058 | SCV001358170 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-17 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with lysine at codon 2928 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 not been identified 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. |
Sema4, |
RCV000563058 | SCV002527953 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-25 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003459307 | SCV004204479 | uncertain significance | Familial cancer of breast | 2023-10-22 | criteria provided, single submitter | clinical testing |