Submissions for variant NM_000051.4(ATM):c.4042T>C (p.Leu1348=)

gnomAD frequency: 0.00599  dbSNP: rs56355831

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001080467	SCV000153881	benign	Ataxia-telangiectasia syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162577	SCV000212993	benign	Hereditary cancer-predisposing syndrome	2014-07-22	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Color Diagnostics, LLC DBA Color Health	RCV000162577	SCV000682179	benign	Hereditary cancer-predisposing syndrome	2015-05-18	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679118	SCV000805551	benign	not specified	2017-06-21	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000119160	SCV001143107	benign	not provided	2019-05-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001080467	SCV001262664	benign	Ataxia-telangiectasia syndrome	2017-04-28	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000119160	SCV001471474	benign	not provided	2020-03-20	criteria provided, single submitter	clinical testing
GeneDx	RCV000119160	SCV001850526	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 17333338)
Genetic Services Laboratory, University of Chicago	RCV000679118	SCV002067015	benign	not specified	2017-10-09	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225351	SCV002504708	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000679118	SCV004027221	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492512	SCV004240658	benign	Breast and/or ovarian cancer	2022-11-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589583	SCV005083951	benign	Familial cancer of breast	2024-05-16	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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000679118	SCV001554329	benign	not specified		no assertion criteria provided	clinical testing	The ATM p.Leu1348= variant was identified in 3 of 54 proband chromosomes (frequency: 0.06) from Moroccan individuals or families with AT (Ataxia-Telangiectasia) (Jeddane_2013_23322442). The variant was also identified in dbSNP (ID: rs56355831) “With Benign allele”, ClinVar (classified benign by Invitae and Ambry Genetics), Clinvitae (2x), LOVD 3.0 (1x), and was not identified in GeneInsight-COGR, Cosmic, or MutDB databases. The variant was identified in control databases in 505 (5 homozygous) of 274492 chromosomes at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 448 (5 homozygous) of 24030 chromosomes (freq: 0.02), Other in 11 of 6442 chromosomes (freq: 0.002), Latino in 40 of 34398 chromosomes (freq: 0.001), European Non-Finnish in 6 of 124160 chromosomes (freq: 0.00005), while not observed in the Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The p.Leu1348= 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.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000119160	SCV001905758	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000679118	SCV001972151	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000679118	SCV002033860	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000679118	SCV002035973	benign	not specified		no assertion criteria provided	clinical testing