ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1444A>C (p.Lys482Gln) (rs202173660)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000211962 SCV000149051 uncertain significance not provided 2018-09-06 criteria provided, single submitter clinical testing This variant is denoted ATM c.1444A>C at the cDNA level, p.Lys482Gln (K482Q) at the protein level, and results in the change of a Lysine to a Glutamine (AAA>CAA). This variant has been observed in individuals with breast cancer and colon cancer, but was also present in healthy control populations (Tung 2015, Decker 2017, Tiao 2017, Yurgelun 2017, Cock-Rada 2018, Hauke 2018). ATM Lys482Gln was observed at an allele frequency of 0.02% (22/111630) in individuals of European ancestry in large population cohorts (Lek 2016). ATM Lys482Gln is not located in a known functional domain. In silico analysis, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether ATM Lys482Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115142 SCV000172911 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-13 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000197378 SCV000254060 likely benign Ataxia-telangiectasia syndrome 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000115142 SCV000537540 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-07 criteria provided, single submitter clinical testing
Counsyl RCV000197378 SCV000800380 uncertain significance Ataxia-telangiectasia syndrome 2018-06-01 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115142 SCV000821831 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000197378 SCV000838488 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000211962 SCV000840917 uncertain significance not provided 2018-04-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779759 SCV000916535 uncertain significance not specified 2017-09-28 criteria provided, single submitter clinical testing Variant summary: The ATM c.1444A>C (p.Lys482Gln) variant causes a missense change involving the alteration of a conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). The variant was found in the control population dataset of gnomAD in 25/246152 control chromosomes at a frequency of 0.0001016, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005). This variant was found in HBOC, CRC, and Mllerian adenosarcoma patients without strong evidence for causality (Cock-Rada_2017, Yurgelun_2017, Howitt_2015). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS, until more definitive clinical and functional studies become available.

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