ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6572+1G>A (rs587779856)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212046 SCV000149140 pathogenic not provided 2014-03-17 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.6572+1G>A or IVS45+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 45 of the ATM gene. The variant destroys a canonical splice donor 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, also reported in intron 47 using alternative nomenclature, has been reported in a patient with Ataxia Telangiectasia (A-T)who carried a second ATM variant and is considered pathogenic (Birrell 2005). A single variant in the ATM gene has been estimated to increase the relative risk of female breast cancer about 2-fold over the general population (Thompson 2005, Renwick 2006) resulting in a lifetime risk of approximately 25-30%. According to one study, breast cancer risk in women under age 50 who carry one ATM variant is nearly 5 times the age-matched general population risk which translates to approximately a 10% risk (Thompson 2005). This study of 1160 ATM carriers also reported evidence of increased risk for colon cancer. In a recent study of 166 unrelated familial pancreatic cancer patients, 2.4% were identified as carriers of one ATM variant, and in families with 3 or more cases of pancreatic cancer, 4.6% carried an ATM variant (Roberts 2012). Ataxia-Telangiectasia (A-T) is an autosomal recessive condition caused by two mutations (one affecting each allele) in the ATM gene. This multisystem disorder is characterized by progressive neurodegeneration, telangiectasias, immunodeficiency, and increased cancer risks. If an ATM variant carrier'spartner is also heterozygous for an ATM variant, the risk to have a child with A-T is 25% with each pregnancy.
Ambry Genetics RCV000115231 SCV000218014 likely pathogenic Hereditary cancer-predisposing syndrome 2016-03-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Alterations at the canonical donor/acceptor sites (+/- 1, 2) without splicing assay data in support of pathogenicity,Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes) ,Other data supporting pathogenic classification
Counsyl RCV000410003 SCV000486187 likely pathogenic Ataxia-telangiectasia syndrome 2016-04-13 criteria provided, single submitter clinical testing

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