ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6239A>G (p.Tyr2080Cys)

dbSNP: rs587779855
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212043 SCV000149138 uncertain significance not provided 2015-09-16 criteria provided, single submitter clinical testing This variant is denoted ATM c.6239A>G at the cDNA level, p.Tyr2080Cys (Y2080C) at the protein level, and results in the change of a Tyrosine to a Cysteine (TAT>TGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Tyr2080Cys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Tyrosine and Cysteine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Tyr2080Cys occurs at a position that is conserved across species and is located in the FAT domain (Stracker 2013, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM Tyr2080Cys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115229 SCV000184429 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-30 criteria provided, single submitter clinical testing The p.Y2080C variant (also known as c.6239A>G), located in coding exon 42 of the ATM gene, results from an A to G substitution at nucleotide position 6239. The tyrosine at codon 2080 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000115229 SCV000682317 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-06 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 2080 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). To our knowledge, functional studies have not been reported for this variant. In a large international case-control study, this variant was reported in 2/60466 breast cancer cases and 0/53461 controls (PMID: 33471991). 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 (formerly Invitae), Labcorp RCV000627951 SCV000748837 uncertain significance Ataxia-telangiectasia syndrome 2024-12-29 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2080 of the ATM protein (p.Tyr2080Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 127424). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATM protein function with a negative predictive value of 95%. 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.
Baylor Genetics RCV003460808 SCV004204490 uncertain significance Familial cancer of breast 2023-12-20 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.