ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5618G>A (p.Cys1873Tyr)

gnomAD frequency: 0.00010  dbSNP: rs587782239
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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 RCV000222325 SCV000277450 likely benign Hereditary cancer-predisposing syndrome 2018-02-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000627966 SCV000748852 uncertain significance Ataxia-telangiectasia syndrome 2023-10-15 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1873 of the ATM protein (p.Cys1873Tyr). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 233138). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Color Diagnostics, LLC DBA Color Health RCV000222325 SCV000904871 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-17 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tyrosine at codon 1873 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/31378 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics RCV003469066 SCV004208163 uncertain significance Familial cancer of breast 2023-11-18 criteria provided, single submitter clinical testing

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