Submissions for variant NM_000051.4(ATM):c.4980C>T (p.Asn1660=)

gnomAD frequency: 0.00019  dbSNP: rs144338238

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084181	SCV000166114	likely benign	Ataxia-telangiectasia syndrome	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000212026	SCV000167092	benign	not specified	2014-01-24	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	RCV000123749	SCV000212916	likely benign	Hereditary cancer-predisposing syndrome	2014-06-23	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.
Color Diagnostics, LLC DBA Color Health	RCV000123749	SCV000537419	likely benign	Hereditary cancer-predisposing syndrome	2015-07-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588006	SCV000694296	benign	not provided	2017-07-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000588006	SCV000805575	likely benign	not provided	2017-08-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588006	SCV001249807	likely benign	not provided	2021-12-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798394	SCV002042257	likely benign	Breast and/or ovarian cancer	2022-08-15	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212026	SCV002065098	likely benign	not specified	2018-02-26	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225391	SCV002504724	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000123749	SCV002527767	likely benign	Hereditary cancer-predisposing syndrome	2021-06-03	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212026	SCV002760577	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589604	SCV005084044	benign	Familial cancer of breast	2024-05-21	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	RCV001358457	SCV001554197	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM p.Asn1660 variant was identified in the literature however the frequency of this variant in an affected population was not provided. The variant was present in 1 of 562 control chromosomes (frequency: 0.002) from healthy individuals (Skowronska 2012). The variant was also identified in dbSNP (ID: rs144338238) as With Likely benign allele, ClinVar (classified as benign by GeneDx; classified as likely benign by Invitae, Ambry Genetics, Color Genomics), databases. The variant was not identified in GeneInsight-COGR, Cosmic, MutDB, LOVD 3.0, ATM-LOVD, databases. The variant was identified in control databases in 68 of 276658 chromosomes at a frequency of 0.000246 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The p.Asn1660= 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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000588006	SCV001809633	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000588006	SCV001905954	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000588006	SCV001931914	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000588006	SCV001959363	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000588006	SCV001975463	likely benign	not provided		no assertion criteria provided	clinical testing