Submissions for variant NM_000051.4(ATM):c.2606C>G (p.Ala869Gly)

gnomAD frequency: 0.00013  dbSNP: rs145513717

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164332	SCV000214963	uncertain significance	Hereditary cancer-predisposing syndrome	2022-12-20	criteria provided, single submitter	clinical testing	The p.A869G variant (also known as c.2606C>G), located in coding exon 16 of the ATM gene, results from a C to G substitution at nucleotide position 2606. The alanine at codon 869 is replaced by glycine, an amino acid with similar properties. This variant has been identified in an individual with pancreatic cancer (Chaffee KG et al. Genet Med, 2018 01;20:119-127). 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476653	SCV000547002	uncertain significance	Ataxia-telangiectasia syndrome	2024-01-30	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 869 of the ATM protein (p.Ala869Gly). This variant is present in population databases (rs145513717, gnomAD 0.05%). 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: 184982). 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.
GeneDx	RCV000479991	SCV000570502	uncertain significance	not provided	2023-10-09	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28726808)
Mendelics	RCV000476653	SCV000838508	uncertain significance	Ataxia-telangiectasia syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164332	SCV000911326	likely benign	Hereditary cancer-predisposing syndrome	2017-01-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225480	SCV002505328	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465546	SCV002760535	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003467290	SCV004207727	uncertain significance	Familial cancer of breast	2024-03-29	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003467290	SCV005083910	likely benign	Familial cancer of breast	2024-05-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Natera, Inc.	RCV000476653	SCV002076320	uncertain significance	Ataxia-telangiectasia syndrome	2020-03-06	no assertion criteria provided	clinical testing