ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.8066A>G (p.Glu2689Gly)

dbSNP: rs759779781
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000580705 SCV000682452 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000627935 SCV000748820 uncertain significance Ataxia-telangiectasia syndrome 2024-05-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2689 of the ATM protein (p.Glu2689Gly). This variant is present in population databases (rs759779781, gnomAD 0.0009%). 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: 489594). 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 tolerated. 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.
Mendelics RCV000627935 SCV001138575 uncertain significance Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580705 SCV001189638 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-23 criteria provided, single submitter clinical testing The p.E2689G variant (also known as c.8066A>G), located in coding exon 54 of the ATM gene, results from an A to G substitution at nucleotide position 8066. The glutamic acid at codon 2689 is replaced by glycine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with bilateral invasive ductal carcinoma at age 45 years, from a cohort of 113 Italian probands without a BRCA1 or BRCA2 mutation, using a 25 gene cancer panel (Germani A et al. J Clin Med, 2020 Sep;9:). This amino acid position is not well 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.
GeneDx RCV004760629 SCV005372058 uncertain significance not provided 2023-07-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with breast cancer (Germani et al., 2020); This variant is associated with the following publications: (PMID: 32957588)

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