Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216785 | SCV000276152 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-25 | criteria provided, single submitter | clinical testing | The p.K2589E variant (also known as c.7765A>G), located in coding exon 51 of the ATM gene, results from an A to G substitution at nucleotide position 7765. The lysine at codon 2589 is replaced by glutamic acid, an amino acid with similar properties. This alteration was not observed in 7,051 unselected female breast cancer patients or 11,241 female controls of Japanese ancestry. In addition, it was not observed in unselected male breast cancer patients and was observed with an allele frequency of 0.0001 in 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is well conserved in available vertebrate species. 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. |
Labcorp Genetics |
RCV001853578 | SCV002311537 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-04-05 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 232103). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 2589 of the ATM protein (p.Lys2589Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. |