ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6413_6414GA[1] (p.Glu2139fs) (rs863225466)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507916 SCV000602578 pathogenic not specified 2017-03-16 criteria provided, single submitter clinical testing
GeneDx RCV000236729 SCV000293438 pathogenic not provided 2018-05-04 criteria provided, single submitter clinical testing This deletion of two nucleotides in ATM is denoted c.6415_6416delGA at the cDNA level and p.Glu2139IlefsX6 (E2139IfsX6) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CAGA[delGA]ATTC. The deletion causes a frameshift which changes a Glutamic Acid to an Isoleucine at codon 2139, and creates a premature stop codon at position 6 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. ATM c.6415_6416delGA, published as c.6412delAG using alternate nomenclature, has been observed in at least two individuals/families in the compound heterozygous state. One of these individuals exhibited an atypical AT phenotype and ATM protein expression and phosphorylation were reduced in cells derived from this patient (McConville 1996, Stewart 2001, Leong 2003, Sutton 2004). We consider this variant to be pathogenic.
Invitae RCV000202419 SCV000257479 pathogenic Ataxia-telangiectasia syndrome 2018-12-30 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 44 of the ATM mRNA (c.6415_6416delAG), causing a frameshift at codon 2139. This creates a premature translational stop signal (p.Glu2139Ilefs*6) and is expected to result in an absent or disrupted protein product. Truncating variants in ATM are known to be pathogenic. This particular truncation has been reported in patients affected with ataxia telangiectasia (PMID: 8755918). This variant is also known as 6412delAG. For these reasons, this variant has been classified as Pathogenic.

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