ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6188G>A (p.Gly2063Glu) (rs866290641)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484938 SCV000568328 uncertain significance not provided 2017-03-09 criteria provided, single submitter clinical testing The G2063E variant in the ATM gene has been reported in the homozygous state in at least two Turkish individuals with ataxia-telangiectasia (A-T); however, their presentation was noted to be distinct from other A-T patients in that it was slowly progressive with normal immune status (Becker-Catania et al., 2000; Buzin et al., 2003; Chun et al., 2003; Sanal et al., 2004). Cell lines from the homozygous A-T patients were reported to be radiosensitive with reduced ATM protein levels and 35% kinase activity (Becker-Catania et al., 2000; Chun et al., 2003; Butch et al., 2004). However, an in vitro functional study classified this variant as ‘operationally neutral’ with normal protein expression and normal ATM kinase activity (Mitui et al., 2009). The G2063E variant was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glycine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. The G2063E variant occurs at a position that is conserved across species and is located in the FAT domain (Stracker et al., 2013). Based on currently available evidence, we consider G2063E to be a variant of uncertain significance.

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