ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8428A>C (p.Lys2810Gln) (rs730881325)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569229 SCV000660450 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000569229 SCV000682488 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-03 criteria provided, single submitter clinical testing
Counsyl RCV000168380 SCV000793703 uncertain significance Ataxia-telangiectasia syndrome 2017-08-29 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764950 SCV000896122 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000159661 SCV000209657 uncertain significance not provided 2018-07-27 criteria provided, single submitter clinical testing This variant is denoted ATM c.8428A>C at the cDNA level, p.Lys2810Gln (K2810Q) at the protein level, and results in the change of a Lysine to a Glutamine (AAA>CAA). This variant was observed in an individual with early-onset colorectal cancer and polyps but has also been seen in healthy controls (de Voer 2016, Tiao 2017). ATM Lys2810Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). ATM Lys2810Gln is located in the kinase 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 Lys2810Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GeneKor MSA RCV000569229 SCV000821878 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000168380 SCV000219071 uncertain significance Ataxia-telangiectasia syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 2810 of the ATM protein (p.Lys2810Gln). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is present in population databases (rs730881325, ExAC 0.006%). This variant has been reported in an individual affected with colorectal cancer (PMID: 26901136). ClinVar contains an entry for this variant (Variation ID: 181898). 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 tolerated, 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.

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