Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024909 | SCV001187004 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-06 | criteria provided, single submitter | clinical testing | The p.E2039V variant (also known as c.6116A>T), located in coding exon 41 of the ATM gene, results from an A to T substitution at nucleotide position 6116. The glutamic acid at codon 2039 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is highly 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 |
RCV001224213 | SCV001396397 | likely pathogenic | Ataxia-telangiectasia syndrome | 2023-06-30 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Glu2039 amino acid residue in ATM. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19431188, 19781682, 22071889, 28975465). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 417621). This missense change has been observed in individuals with ataxia-telangiectasia (PMID: 26896183). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 2039 of the ATM protein (p.Glu2039Val). |
| Sanfordhealth- |
RCV000464903 | SCV000537889 | uncertain significance | Familial cancer of breast | no assertion criteria provided | clinical testing | This VUS was reported by GeneDx 5/22/2015. VUS present in woman (pt A4 my pedigree) who had breast ca age 29 yrs. VUS also present in her mother who had breast ca age 51 years. Patient A4 has a maternal first cousin A7 who had colon cancer age 22 years and testicular cancer 22 years. Another individual C5 in maternal family had pancreatic cancer age 72 years. |