ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5319+6_5319+7del (rs777478613)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228041 SCV000282987 uncertain significance Ataxia-telangiectasia syndrome 2019-10-23 criteria provided, single submitter clinical testing This sequence change falls in intron 35 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein, but it affects a nucleotide within the consensus splice site of the intron. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 236735). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.
GeneDx RCV000485197 SCV000567925 uncertain significance not provided 2018-09-19 criteria provided, single submitter clinical testing This variant is denoted ATM c.5319+6_5319+7delTT or IVS35+6_IVS35+7delTT and consists of a deletion of two nucleotides at the +6 to +7 position in intron 35 of the ATM gene. The normal sequence with the bases that are deleted in brackets is tctc[deltt]aagt. In-silico analyses, which include splice predictors and evolutionary conservation, are uninformative in their assessment as to whether or not the variant is damaging. ATM c.5319+6_5319+7delTT was not observed at a significant frequency in large population cohorts (Lek 2016). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. Based on currently available evidence, it is unclear whether ATM c.5319+6_5319+7delTT is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000228041 SCV000791315 uncertain significance Ataxia-telangiectasia syndrome 2017-05-08 criteria provided, single submitter clinical testing
Color RCV000771466 SCV000903904 likely benign Hereditary cancer-predisposing syndrome 2016-11-22 criteria provided, single submitter clinical testing

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