ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2553T>G (p.Asp851Glu) (rs1064793513)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483479 SCV000566301 uncertain significance not provided 2017-12-20 criteria provided, single submitter clinical testing This variant is denoted ATM c.2553T>G at the cDNA level, p.Asp851Glu (D851E) at the protein level, and results in the change of an Aspartic Acid to a Glutamic Acid (GAT>GAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Asp851Glu was not observed at a significant allele frequency in large population cohorts (Lek 2016). ATM Asp851Glu is not located in a known functional domain. In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether ATM Asp851Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000569986 SCV000665302 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000821523 SCV000962282 uncertain significance Ataxia-telangiectasia syndrome 2018-08-16 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 851 of the ATM protein (p.Asp851Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 418904). 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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