ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2838+4A>G (rs876659907)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222111 SCV000276849 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Color RCV000222111 SCV000687421 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779800 SCV000916604 uncertain significance not specified 2018-10-29 criteria provided, single submitter clinical testing Variant summary: ATM c.2838+4A>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: three predict the variant weakens a 5' donor site; while two predict the variant abolishes this 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 246006 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2838+4A>G in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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