Submissions for variant NM_000051.4(ATM):c.8730C>G (p.Leu2910=)

gnomAD frequency: 0.00001  dbSNP: rs551041839

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084626	SCV000166149	benign	Ataxia-telangiectasia syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000164225	SCV000214846	likely benign	Hereditary cancer-predisposing syndrome	2014-10-24	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.
GeneDx	RCV000444064	SCV000512184	benign	not specified	2015-08-14	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.
Color Diagnostics, LLC DBA Color Health	RCV000164225	SCV000682510	likely benign	Hereditary cancer-predisposing syndrome	2015-07-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000444064	SCV000694384	likely benign	not specified	2019-10-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000444064	SCV000805631	benign	not specified	2017-05-15	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225392	SCV002504784	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000164225	SCV002527920	benign	Hereditary cancer-predisposing syndrome	2021-12-08	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000444064	SCV002760708	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149834	SCV003837978	likely benign	Breast and/or ovarian cancer	2021-06-16	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315811	SCV004017325	benign	Familial cancer of breast	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003315811	SCV005085770	benign	Familial cancer of breast	2024-06-20	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	RCV001356058	SCV001551118	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM p.Leu2910= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Cosmic, MutDB, LOVD 3.0, or in ATM-LOVD databases. The variant was identified in dbSNP (ID: rs551041839) as "With Likely benign allele", ClinVar (classified as benign by Invitae, GeneDx; as likely benign by Ambry Genetics, Color Genomics, Integrated Genetics/Laboratory Corporation of America), and Clinvitae databases. The variant was identified in control databases in 153 of 246230 chromosomes (1 homozygous) at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include South Asian in 151 of 30782 chromosomes (freq: 0.004905), and Ashkenazi Jewish in 2 of 9848 chromosomes (freq: 0.0002) while the variant was not observed in the African, Other, Latino, European, East Asian, or Finnish populations. The p.Leu2910= 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 the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573723	SCV001800012	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000444064	SCV001808788	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001573723	SCV001953520	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573723	SCV001965211	likely benign	not provided		no assertion criteria provided	clinical testing