Submissions for variant NM_000051.4(ATM):c.198A>G (p.Lys66=)

gnomAD frequency: 0.00006  dbSNP: rs540920248

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000122830	SCV000166087	benign	Ataxia-telangiectasia syndrome	2025-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000211943	SCV000209602	benign	not specified	2014-09-26	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	RCV000159617	SCV000213024	likely benign	Hereditary cancer-predisposing syndrome	2014-07-27	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	RCV000159617	SCV000682020	likely benign	Hereditary cancer-predisposing syndrome	2015-08-07	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798390	SCV002041939	likely benign	Breast and/or ovarian cancer	2020-02-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000211943	SCV002066509	likely benign	not specified	2018-08-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000159617	SCV002533999	likely benign	Hereditary cancer-predisposing syndrome	2020-05-27	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV003390809	SCV004131391	likely benign	not provided	2022-07-01	criteria provided, single submitter	clinical testing	ATM: BP4, BP7
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000159617	SCV004228165	benign	Hereditary cancer-predisposing syndrome	2023-10-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000211943	SCV005039189	likely benign	not specified	2024-03-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589595	SCV005084385	benign	Familial cancer of breast	2024-04-18	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	RCV001358207	SCV001553880	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM p.Lys66= variant was not identified in the literature. The variant was identified in dbSNP (rs540920248) as “with likely benign allele”, ClinVar (interpreted as "likely benign" by Invitae and 3 others) and LOVD 3.0 (observed 1x). The variant was identified in control databases in 24 of 275,020 chromosomes at a frequency of 0.00009 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 1 of 125,518 chromosomes (freq: 0.000008), Ashkenazi Jewish in 23 of 10,074 chromosomes (freq: 0.002), but not in the African, Other, Latino, East Asian, Finnish and South Asian populations. The p.Lys66= 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. The variant occurs outside of the splicing consensus sequence, and 4 of 4 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.
PreventionGenetics, part of Exact Sciences	RCV004551195	SCV004768351	likely benign	ATM-related disorder	2020-02-25	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).