ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8325del (p.Ile2776fs) (rs886039623)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255611 SCV000322542 pathogenic not provided 2017-11-29 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.8325delC at the cDNA level and p.Ile2776LeufsX30 (I2776LfsX30) at the protein level. The normal sequence, with the base that is deleted in brackets, is TCCC[delC]ATTG. The deletion causes a frameshift which changes an Isoleucine to a Leucine at codon 2776, and creates a premature stop codon at position 30 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 8325delC, published as ATM 8322*>-C using alternate nomenclature, has been observed in at least one individual with breast cancer (Aloraifi 2015). We consider this variant to be pathogenic.
Ambry Genetics RCV000494589 SCV000581457 pathogenic Hereditary cancer-predisposing syndrome 2016-02-25 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV001061492 SCV001226236 pathogenic Ataxia-telangiectasia syndrome 2019-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile2776Leufs*30) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast cancer (PMID: 28779002, 26094658). This variant is also known as "p.X2774X/c.8322*>-C" in the literature. ClinVar contains an entry for this variant (Variation ID: 265556). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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