ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1215del (p.Asn405fs) (rs1555069815)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000659279 SCV000781079 pathogenic Familial cancer of breast 2016-11-01 criteria provided, single submitter clinical testing
Color RCV000771728 SCV000904385 pathogenic Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
Counsyl RCV000576782 SCV000678173 likely pathogenic Ataxia-telangiectasia syndrome 2017-02-03 criteria provided, single submitter clinical testing
GeneDx RCV000657201 SCV000778927 pathogenic not provided 2018-05-14 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.1215delT at the cDNA level and p.Asn405LysfsX15 (N405KfsX15) at the protein level. The normal sequence, with the base that is deleted in brackets, is AGAA[delT]GATT. The deletion causes a frameshift, which changes an Asparagine to a Lysine at codon 405 and creates a premature stop codon at position 15 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.1215delT has been been reported in an individual with triple negative breast cancer and an individual with male breast cancer (Couch 2015, Fostira 2018). This variant was also observed in a patient with ataxia telangiectasia who carried a second ATM variant, though phase was not confirmed, who had very low ATM protein levels (Nahas 2009). Based on currently available evidence, we consider this deletion to be pathogenic.
Invitae RCV000576782 SCV000825167 pathogenic Ataxia-telangiectasia syndrome 2018-12-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn405Lysfs*15) 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 an individual affected with breast cancer and in a family affected with ataxia telangiectasia (PMID: 25452441, 16387360). ClinVar contains an entry for this variant (Variation ID: 487449). 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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