ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5675-4T>A (rs56075338)

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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 RCV000214255 SCV000274949 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000214255 SCV000910864 likely benign Hereditary cancer-predisposing syndrome 2015-06-09 criteria provided, single submitter clinical testing
GeneDx RCV000590713 SCV000569622 uncertain significance not provided 2018-07-06 criteria provided, single submitter clinical testing This variant is denoted ATM c.5675-4T>A or IVS37-4T>A and consists of a T>A nucleotide substitution at the -4 position of intron 37 of the ATM gene. In silico analyses, which include splice predictors and evolutionary conservation, are inconsistent in their assessment as to whether or not the variant is damaging.? This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. This variant was observed at an allele frequency of 0.15% (47/30,736) in individuals of South Asian ancestry in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether ATM c.5675-4T>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000590713 SCV000694306 likely benign not provided 2016-09-30 criteria provided, single submitter clinical testing Variant summary: The ATM c.5675-4T>A variant involves the alteration of a non-conserved intronic nucleotide with 4/5 splice prediction tools predicting no significant impact on normal splicing and ESE finder predicting the creation of an ESE binding site, however, these predictions have yet to be functionally assessed. The variant of interest has been observed in the large, broad control population, ExAC, with an allele frequency of 35/116558 (1/3330, 1 homozygote), predominantly in the South Asian cohort, 33/15866 (1/480), which exceeds the estimated maximal expected allele frequency for a pathogenic ATM variant of 1/999. Therefore, suggesting the variant is a common polymorphism found in population(s) of South Asian origin. The variant of interest, to our knowledge, has not been reported in affected individuals via publications, however, clinical diagnostic laboratories have cited the variant as "likely benign" or "uncertain significance." Therefore, the variant of interest has been classified as Likely Benign.
Invitae RCV000196649 SCV000252966 likely benign Ataxia-telangiectasia syndrome 2017-05-30 criteria provided, single submitter clinical testing

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