Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569472 | SCV000667921 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-04-25 | criteria provided, single submitter | clinical testing | The p.D2569G variant (also known as c.7706A>G), located in coding exon 51 of the ATM gene, results from an A to G substitution at nucleotide position 7706. The aspartic acid at codon 2569 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. 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 |
RCV003605646 | SCV004464222 | uncertain significance | Ataxia-telangiectasia syndrome | 2023-05-07 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 482595). 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 aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2569 of the ATM protein (p.Asp2569Gly). |
| Institute for Biomarker Research, |
RCV000569472 | SCV002050284 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-23 | no assertion criteria provided | clinical testing |