ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8520G>C (p.Leu2840Phe) (rs752652869)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219341 SCV000274172 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000219341 SCV000682492 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000204493 SCV000914481 uncertain significance Ataxia-telangiectasia syndrome 2018-12-03 criteria provided, single submitter clinical testing The ATM c.8520G>C (p.Leu2840Phe) missense variant has been reported in a homozygous state in one study in one individual with classical ataxia telangiectasia (Carney et al. 2012). Functional studies revealed the individual had 5% residual ATM protein expression with no residual enzyme activity. Control data are unavailable for p.Leu2840Phe variant, which is reported at a frequency of 0.000097 in the African population of the Exome Aggregation Consortium but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the evidence, the p.Leu2840Phe variant is classified as a variant of unknown significance but suspicious for pathogenicity for ataxia telangiectasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000204493 SCV000262318 uncertain significance Ataxia-telangiectasia syndrome 2018-06-26 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 2840 of the ATM protein (p.Leu2840Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (ExAC 0.01%). An individual affected with ataxia telangiectasia has been reported to be homozygous for this variant (PMID: 22649200). ClinVar contains an entry for this variant (Variation ID: 221124). An experimental study has suggested that this missense change results in loss of ATM protein kinase activity and lower ATM protein expression in comparison with wild type (PMID: 22649200). 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.