ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.902G>A (p.Gly301Asp) (rs202208861)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168392 SCV000219085 uncertain significance Ataxia-telangiectasia syndrome 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 301 of the ATM protein (p.Gly301Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs202208861, ExAC 0.008%). This variant has been reported in an individual affected with breast cancer (PMID: 19781682). ClinVar contains an entry for this variant (Variation ID: 188359). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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.
Ambry Genetics RCV000221865 SCV000273019 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
GeneDx RCV000585382 SCV000564611 uncertain significance not provided 2018-12-27 criteria provided, single submitter clinical testing This variant is denoted ATM c.902G>A at the cDNA level, p.Gly301Asp (G301D) at the protein level, and results in the change of a Glycine to an Aspartic Acid (GGT>GAT). This variant was reported in several individuals with breast cancer (Tavtigian 2009, Decker 2017, Hauke 2018), but has also been observed in control subjects from a CLL case-control study (Tiao 2017). ATM Gly301Asp was observed at an allele frequency of 0.012% (15/126,334) in individuals of European ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether ATM Gly301Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585382 SCV000692730 uncertain significance not provided 2018-02-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000168392 SCV000743719 uncertain significance Ataxia-telangiectasia syndrome 2016-10-04 criteria provided, single submitter clinical testing
Counsyl RCV000168392 SCV000789258 uncertain significance Ataxia-telangiectasia syndrome 2017-01-20 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000585382 SCV000805636 uncertain significance not provided 2018-01-17 criteria provided, single submitter clinical testing
Color RCV000221865 SCV000903251 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000168392 SCV000732988 uncertain significance Ataxia-telangiectasia syndrome no assertion criteria provided clinical testing

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