Submissions for variant NM_000051.4(ATM):c.370A>G (p.Ile124Val)

gnomAD frequency: 0.00215  dbSNP: rs148590073

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000679113	SCV000149087	likely benign	not provided	2021-03-14	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22952040, 11505391, 17333338, 19781682, 12673804, 25980754, 12552559)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000122843	SCV000166101	benign	Ataxia-telangiectasia syndrome	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000115178	SCV000186563	likely benign	Hereditary cancer-predisposing syndrome	2018-09-07	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.
PreventionGenetics, part of Exact Sciences	RCV000254228	SCV000301663	likely benign	not specified		criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000115178	SCV000682156	likely benign	Hereditary cancer-predisposing syndrome	2015-03-04	criteria provided, single submitter	clinical testing
Counsyl	RCV000122843	SCV000797247	likely benign	Ataxia-telangiectasia syndrome	2018-01-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000254228	SCV000916543	benign	not specified	2017-09-07	criteria provided, single submitter	clinical testing	Variant summary: The ATM c.370A>G (p.Ile124Val) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant . This variant was found in 93/126020 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.007634 (79/10348). This frequency is about 8 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. This missense mutation has been observed in cancer patients without significant evidence for a causal role in disease (e.g. co-segregation data were not provided). In at least one ataxia-telangiectasia patient the variant co-occured with two other mutations predicted to be causative for ataxia-telangiectasia (Buzin_2003). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign, and most peer reviewed publications consider the variant a polymorphism. Taken together, this variant is classified as benign.
Athena Diagnostics	RCV000679113	SCV001143105	benign	not provided	2019-06-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000679113	SCV001148398	benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	ATM: BP1, BP2, BP4, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000679113	SCV001157708	benign	not provided	2021-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000122843	SCV001260304	benign	Ataxia-telangiectasia syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Genetic Services Laboratory, University of Chicago	RCV000254228	SCV002070846	likely benign	not specified	2021-07-23	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000115178	SCV002536573	benign	Hereditary cancer-predisposing syndrome	2020-09-10	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315635	SCV004017203	benign	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000679113	SCV004220995	benign	not provided	2019-06-30	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003315635	SCV005083926	benign	Familial cancer of breast	2024-04-19	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. 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].
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000254228	SCV005090413	benign	not specified	2024-07-31	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000679113	SCV002034376	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000679113	SCV002037406	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000679113	SCV002037917	likely benign	not provided		no assertion criteria provided	clinical testing