ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.610G>A (p.Gly204Arg) (rs147915571)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115224 SCV000184444 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000235097 SCV000780399 uncertain significance not provided 2018-02-28 criteria provided, single submitter clinical testing
Color RCV000115224 SCV000537552 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-11 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000235097 SCV000861881 uncertain significance not provided 2018-06-11 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764935 SCV000896107 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000235097 SCV000149133 uncertain significance not provided 2018-03-14 criteria provided, single submitter clinical testing This variant is denoted ATM c.610G>A at the cDNA level, p.Gly204Arg (G204R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>AGA). This variant has been observed in individuals with breast and/or ovarian cancer, in an individual with rhabdomyosarcoma, and in an individual with chronic lymphocytic leukemia (Zhang 2015, Nadeu 2016, Decker 2017, Singh 2018). ATM Gly204Arg was observed at an allele frequency of 0.01% (27/276,836) 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 Gly204Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000122868 SCV000166126 uncertain significance Ataxia-telangiectasia syndrome 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 204 of the ATM protein (p.Gly204Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs147915571, ExAC 0.03%). This variant has been observed in an individual affected with chronic lymphocytic leukemia (PMID: 26837699) and several individuals affected with breast and/or ovarian cancer, as well as an unaffected individual (PMID: 28779002, 29470806). ClinVar contains an entry for this variant (Variation ID: 127419). 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: "Possibly 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.
PreventionGenetics RCV000235097 SCV000805595 uncertain significance not provided 2017-05-30 criteria provided, single submitter clinical testing

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