Submissions for variant NM_000051.4(ATM):c.6888A>T (p.Ala2296=)

gnomAD frequency: 0.00003  dbSNP: rs200735689

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163097	SCV000213605	likely benign	Hereditary cancer-predisposing syndrome	2014-10-22	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000199159	SCV000252976	likely benign	Ataxia-telangiectasia syndrome	2025-01-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163097	SCV000682371	likely benign	Hereditary cancer-predisposing syndrome	2015-12-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589924	SCV000694337	likely benign	not specified	2019-08-20	criteria provided, single submitter	clinical testing
Counsyl	RCV000199159	SCV000788944	likely benign	Ataxia-telangiectasia syndrome	2016-12-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001711326	SCV001946012	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798567	SCV002042812	likely benign	Breast and/or ovarian cancer	2022-07-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163097	SCV002538549	likely benign	Hereditary cancer-predisposing syndrome	2021-08-24	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000589924	SCV004242540	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001711326	SCV005041565	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	ATM: BP4, BP7
Myriad Genetics, Inc.	RCV004589697	SCV005084807	benign	Familial cancer of breast	2024-06-12	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.
Natera, Inc.	RCV000199159	SCV001452126	uncertain significance	Ataxia-telangiectasia syndrome	2020-01-24	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354548	SCV001549193	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM p.Ala2296= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (ID: rs200735689) as "With Uncertain significance allele", ClinVar (classified as likely benign by Invitae, Ambry Genetics, Color and Counsyl; and as uncertain significance by Integrated Genetics/Laboratory Corporation of America). The variant was identified in control databases in 7 of 277030 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 7 of 126558 chromosomes (freq: 0.00006), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Ala2296= 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) 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.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001711326	SCV001979401	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001711326	SCV001980157	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004551384	SCV004770587	likely benign	ATM-related disorder	2020-02-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).