ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5549del (p.Leu1850fs) (rs876658287)

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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 RCV000219889 SCV000273322 pathogenic Hereditary cancer-predisposing syndrome 2018-03-20 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000236989 SCV000292817 pathogenic not provided 2015-04-17 criteria provided, single submitter clinical testing This deletion of one nucleotide in ATM is denoted c.5549delT at the cDNA level and p.Leu1850TyrfsX67 (L1850YfsX67) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATTT[T]ACTC. The deletion causes a frameshift, which changes a Leucine to a Tyrosine at codon 1850, and creates a premature stop codon at position 67 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.5549delT, previously reported as c.5546delT using alternate nomenclature, has been observed in the compound heterozygous state in association with Ataxia-telangiectasia (Sandoval 1999). We consider this variant to be pathogenic.
Counsyl RCV000411540 SCV000486274 likely pathogenic Ataxia-telangiectasia syndrome 2016-04-28 criteria provided, single submitter clinical testing
Invitae RCV000411540 SCV001206115 pathogenic Ataxia-telangiectasia syndrome 2019-11-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1850Tyrfs*67) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs750992549, ExAC 0.002%). This variant has been observed to be homozygous in or in combination with another pathogenic ATM variant in several individuals affected with ataxia-telangiectasia (PMID: 9887333, 16266405, 10817650). It has also been observed as heterozygous in an individual with mesothelioma (PMID: 26556299). This variant is also known as 5546delT in the literature. ClinVar contains an entry for this variant (Variation ID: 229942). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Color RCV000219889 SCV001344865 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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