Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000565674 | SCV000665161 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-17 | criteria provided, single submitter | clinical testing | The p.E2807K variant (also known as c.8419G>A) is located in coding exon 57 of the ATM gene. The glutamic acid at codon 2807 is replaced by lysine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 57. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000565674 | SCV000682486 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-04 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 2807 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may impact RNA splicing, although this prediction has not been confirmed in published RNA studies. To our knowledge, 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. |
Labcorp Genetics |
RCV000702751 | SCV000831619 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-03-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with ATM-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2807 of the ATM protein (p.Glu2807Lys). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 481050). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |