ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3850del (p.Thr1284fs) (rs876660865)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213614 SCV000278636 pathogenic Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000472137 SCV000546898 pathogenic Ataxia-telangiectasia syndrome 2019-12-31 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 26 of the ATM mRNA (c.3850delA), causing a frameshift at codon 1284. This creates a premature translational stop signal (p.Thr1284Glnfs*9) and 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 reported in two individuals affected with ataxia telangiectasia, one of whom was homozygous for this variant (PMID: 9887333, 21833744), and in an individual affected with breast cancer (PMID: 26822949). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000485880 SCV000568320 pathogenic not provided 2018-11-05 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.3850delA at the cDNA level and p.Thr1284GlnfsX9 (T1284QfsX9) at the protein level. The normal sequence, with the base that is deleted in brackets, is TCTA[delA]CAGA. The deletion causes a frameshift which changes a Threonine to a Glutamine at codon 1284, and creates a premature stop codon at position 9 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.3850delA, also reported as 3849delA using alternate nomenclature, has been observed in both the homozygous and compound heterozygous state in individuals with Ataxia-telangiectasia (Sandoval 1999, Soukupova 2011). Additionally, a case-control study identified this variant in the heterozygous state in 1/325 individuals with breast cancer, but not in healthy controls, and this variant was observed in a patient with breast and familial pancreatic cancer (Lhota 2016, West 2018). We consider this variant to be pathogenic.
Counsyl RCV000472137 SCV000678110 pathogenic Ataxia-telangiectasia syndrome 2017-05-23 criteria provided, single submitter clinical testing
Color RCV000213614 SCV001357926 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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