ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.283C>A (p.Gln95Lys) (rs587781545)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000445811 SCV000660459 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000445811 SCV000537548 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764933 SCV000896105 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000159724 SCV000209736 uncertain significance not provided 2018-04-19 criteria provided, single submitter clinical testing This variant is denoted ATM c.283C>A at the cDNA level, p.Gln95Lys (Q95K) at the protein level, and results in the change of a Glutamine to a Lysine (CAG>AAG). This variant has been reported in a pediatric patient with an ependymoma and in an individual with breast cancer (Tung 2015, Zhang 2015). ATM Gln95Lys was observed at an allele frequency of 0.18% (34/18,838) in individuals of East Asian ancestry in large population cohorts (Lek 2016). This variant is located in the region of interaction with p53 & BRCA1 (Tavtigian 2009, 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 Gln95Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000229615 SCV000282913 uncertain significance Ataxia-telangiectasia syndrome 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 95 of the ATM protein (p.Gln95Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (rs587781545, ExAC 0.2%). This variant has been observed in individuals affected with breast cancer (PMID: 28580595). ClinVar contains an entry for this variant (Variation ID: 181957). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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