ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2377-6T>A (rs876660963)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000771210 SCV000903246 likely benign Hereditary cancer-predisposing syndrome 2016-02-10 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000656757 SCV000706976 uncertain significance not provided 2017-04-04 criteria provided, single submitter clinical testing
GeneDx RCV000656757 SCV000278815 uncertain significance not provided 2018-09-07 criteria provided, single submitter clinical testing This variant is denoted ATM c.2377-6T>A or IVS15-6T>A and consists of a T>A nucleotide substitution at the -6 position of intron 15 of the ATM gene. In-silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant, previously reported as IVS17-6T>A using alternate exon numbering, has been observed in at least two individuals with breast cancer (Thorstenson 2003, Hauke 2018). ATM c.2377-6T>A was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether ATM c.2377-6T>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000468699 SCV000547015 uncertain significance Ataxia-telangiectasia syndrome 2018-03-28 criteria provided, single submitter clinical testing This sequence change falls in intron 15 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 234263). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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