Submissions for variant NM_000051.4(ATM):c.5793T>C (p.Ala1931=)

gnomAD frequency: 0.00608  dbSNP: rs3092910

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000119174	SCV000153905	benign	Ataxia-telangiectasia syndrome	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000116428	SCV000167095	benign	not specified	2013-10-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000123752	SCV000212674	likely benign	Hereditary cancer-predisposing syndrome	2015-09-04	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	RCV004549578	SCV000301676	benign	ATM-related disorder	2019-05-15	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Eurofins Ntd Llc (ga)	RCV000116428	SCV000334466	benign	not specified	2015-09-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000416115	SCV000493543	benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	ATM: BP4, BP7, BS1, BS2
Color Diagnostics, LLC DBA Color Health	RCV000123752	SCV000537381	benign	Hereditary cancer-predisposing syndrome	2015-04-10	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000116428	SCV000538368	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not near splice site
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000416115	SCV000602553	benign	not provided	2023-11-07	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000119174	SCV000745129	likely benign	Ataxia-telangiectasia syndrome	2017-06-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000119174	SCV001262765	likely 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Athena Diagnostics	RCV000116428	SCV001879509	benign	not specified	2020-11-25	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000116428	SCV002047318	benign	not specified	2021-09-29	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225339	SCV002504740	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000116428	SCV002760679	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315665	SCV004017081	benign	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003315665	SCV005083984	benign	Familial cancer of breast	2024-05-24	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Genetic Services Laboratory, University of Chicago	RCV000116428	SCV000150353	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
True Health Diagnostics	RCV000123752	SCV000787874	likely benign	Hereditary cancer-predisposing syndrome	2018-02-20	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355317	SCV001550175	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM p.Ala1931= variant was identified in 3 of 572 proband chromosomes (frequency: 0.005) from North American caucasian and American Indian individuals or families with Non-Hodgkin’s Lymphoma, or undisclosed cancer; and was present in 1 of 186 control chromosomes (frequency: 0.005) from healthy individuals (Sipahimalani 2007, Petereit 2013, Thorstenson 2001). Thorstenson et al (2001) showed that ATM shows overall low sequence diversity, when compared across 7 major human populations. The variant was also identified in dbSNP (ID: rs3092910) “With other allele”, ClinVar (classified as benign by Invitae, GeneDx, EGL Genetic Diagnostics (Eurofins Clinical Diagnostics), Color Genomics Inc; and likely benign by Ambry Genetics, Prevention Genetics, Praxis fuer Humangenetik Tuebingen, Lab. for Molecular Medicine Partners HealthCare Personalized Medicine, and Genetic Services Laboratory (U of Chicago)), Clinvitae (5x), and was not identified in Genesight-COGR, Cosmic, MutDB, LOVD 3.0, and ATM-LOVD. The variant was identified in control databases in 1400 (6 homozygous) of 276860 chromosomes at a frequency of 0.005 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: African in 191 (1 homozygous) of 24012 chromosomes (frequency: 008), Other in 27 of 6450 chromosomes (frequency: 004), Latino in 45 of 34376 chromosomes (frequency: 001), European Non-Finnish in 828 (3 homozygous) of 126508 chromosomes (frequency: 007), Ashkenazi Jewish in 31 of 10146 chromosomes (frequency: 003), East Asian in 213 (2 homozygous) of 18848 chromosomes (frequency: 01), European Finnish in 20 of 25750 chromosomes (frequency: 0008), and South Asian in 45 of 30770 chromosomes (frequency: 001). The p.Ala1931= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000116428	SCV001808574	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000416115	SCV001906141	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000416115	SCV001917374	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000416115	SCV001953751	likely benign	not provided		no assertion criteria provided	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000123752	SCV001977068	likely benign	Hereditary cancer-predisposing syndrome	2021-09-27	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000416115	SCV002036170	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000119174	SCV002077326	benign	Ataxia-telangiectasia syndrome	2019-12-02	no assertion criteria provided	clinical testing