ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.7516A>G (p.Arg2506Gly)

gnomAD frequency: 0.00019  dbSNP: rs200441272
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000226242 SCV000283058 uncertain significance Ataxia-telangiectasia syndrome 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2506 of the ATM protein (p.Arg2506Gly). This variant is present in population databases (rs200441272, gnomAD 0.06%). 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: 236775). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV000236767 SCV000292894 uncertain significance not provided 2024-05-09 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Reported in a patient with a family history of breast cancer (PMID: 35534704); This variant is associated with the following publications: (PMID: 23532176, 35534704)
Ambry Genetics RCV000570854 SCV000660522 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-13 criteria provided, single submitter clinical testing The p.R2506G variant (also known as c.7516A>G), located in coding exon 50 of the ATM gene, results from a A to G substitution at nucleotide position 7516. This variant impacts the first base pair of coding exon 50. The arginine at codon 2506 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000570854 SCV000903864 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-05 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 2506 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 ATM-related disorders in the literature. This variant has been identified in 17/281938 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.
Sema4, Sema4 RCV000570854 SCV002538049 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-09 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV004547577 SCV004115291 uncertain significance ATM-related disorder 2023-09-08 criteria provided, single submitter clinical testing The ATM c.7516A>G variant is predicted to result in the amino acid substitution p.Arg2506Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.060% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-108202171-A-G). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/236775/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003463633 SCV004207573 uncertain significance Familial cancer of breast 2024-03-17 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV001535479 SCV001749412 not provided Ataxia-telangiectasia syndrome; Malignant tumor of breast no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 04-20-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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