ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4437-1G>C (rs759520465)

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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 RCV000216400 SCV000275817 pathogenic Hereditary cancer-predisposing syndrome 2018-10-01 criteria provided, single submitter clinical testing
GeneDx RCV000486776 SCV000568323 pathogenic not provided 2017-08-25 criteria provided, single submitter clinical testing This variant is denoted ATM c.4437-1G>C or IVS29-1G>C and consists of a G>C nucleotide substitution at the -1 position of intron 29 of the ATM gene. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant, previously described as IVS31-1G>C by alternate nomenclature, has been reported in the homozygous state in an individual with classical Ataxia-telangiectasia (Mitui 2003). Based on the current evidence, we consider this variant to be pathogenic.
Invitae RCV000530451 SCV000622501 likely pathogenic Ataxia-telangiectasia syndrome 2019-11-11 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 29 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs759520465, ExAC 0.01%). This variant has been reported as homozygous in an individual affected with autosomal recessive ataxia-telangiectasia (PMID: 12815592). This variant is also known as IVS31-1G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 231843). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Counsyl RCV000530451 SCV000798327 likely pathogenic Ataxia-telangiectasia syndrome 2018-03-09 criteria provided, single submitter clinical testing
Color RCV000216400 SCV001340523 likely pathogenic Hereditary cancer-predisposing syndrome 2019-11-25 criteria provided, single submitter clinical testing

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