ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6860G>A (p.Gly2287Glu) (rs1800061)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164364 SCV000214999 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000234176 SCV000283026 uncertain significance Ataxia-telangiectasia syndrome 2018-11-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 2287 of the ATM protein (p.Gly2287Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs1800061, ExAC 0.007%). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 185012). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
GeneDx RCV000485783 SCV000569001 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing This variant is denoted ATM c.6860G>A at the cDNA level, p.Gly2287Glu (G2287E) at the protein level, and results in the change of a Glycine to a Glutamic Acid (GGA>GAA). This variant has been reported in an individual with colorectal cancer (Yurgelun 2017). ATM Gly2287Glu 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 that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Gly2287Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000234176 SCV000799668 uncertain significance Ataxia-telangiectasia syndrome 2018-04-29 criteria provided, single submitter clinical testing
Mendelics RCV000234176 SCV000838582 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000164364 SCV000902931 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing

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