ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7552C>T (p.Pro2518Ser) (rs374876799)

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
Ambry Genetics RCV000159751 SCV000217012 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000159751 SCV000682425 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-15 criteria provided, single submitter clinical testing
Counsyl RCV000469048 SCV000799809 uncertain significance Ataxia-telangiectasia syndrome 2018-05-07 criteria provided, single submitter clinical testing
GeneDx RCV000212071 SCV000209767 uncertain significance not provided 2018-06-14 criteria provided, single submitter clinical testing This variant is denoted ATM c.7552C>T at the cDNA level, p.Pro2518Ser (P2518S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). This variant was observed in at least one individual with colorectal cancer and one individual with breast cancer (Tung 2015, Yurgelun 2017). ATM Pro2518Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the FAT domain (Stracker 2013). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether ATM Pro2518Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000469048 SCV000547058 uncertain significance Ataxia-telangiectasia syndrome 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2518 of the ATM protein (p.Pro2518Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs374876799, ExAC 0.01%). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 181983). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.