ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5618G>A (p.Cys1873Tyr) (rs587782239)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222325 SCV000277450 likely benign Hereditary cancer-predisposing syndrome 2018-02-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene,Co-occurence with mutation in same gene (phase unknown),In silico models in agreement (benign)
Color RCV000222325 SCV000904871 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587287 SCV000694304 uncertain significance not provided 2017-04-06 criteria provided, single submitter clinical testing Variant summary: The c.5618G>A (p.Cys1873Tyr) in ATM gene is a missense change that involves a non-conserved nucleotide and 2/4 in silico tools predict benign outcome. The variant of interest is located outside of any known functional domain. The variant is absent from the control population dataset of ExAC (0/120620chrs tested), but is identified in 3/30954chrs tested of gnomAD dataset. This variant has not, to our knowledge, been reported in affected individuals via published reports, but is cited as VUS by a reputable database/clinical laboratory. Taking together, the variant was classified as VUS.
Invitae RCV000627966 SCV000748852 uncertain significance Ataxia-telangiectasia syndrome 2018-02-19 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 1873 of the ATM protein (p.Cys1873Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 233138). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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