Submissions for variant NM_000051.4(ATM):c.372C>A (p.Ile124=)

gnomAD frequency: 0.00001  dbSNP: rs773495195

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165346	SCV000216070	likely benign	Hereditary cancer-predisposing syndrome	2014-10-14	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	RCV000203984	SCV000259376	likely benign	Ataxia-telangiectasia syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165346	SCV000682158	likely benign	Hereditary cancer-predisposing syndrome	2015-10-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001636702	SCV001849461	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001636702	SCV002048337	likely benign	not provided	2021-08-06	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000165346	SCV002536584	likely benign	Hereditary cancer-predisposing syndrome	2021-02-26	criteria provided, single submitter	curation
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003491897	SCV004240602	likely benign	Breast and/or ovarian cancer	2023-03-13	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589771	SCV005083927	benign	Familial cancer of breast	2024-04-19	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.
True Health Diagnostics	RCV000165346	SCV000787860	likely benign	Hereditary cancer-predisposing syndrome	2017-10-10	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355423	SCV001550305	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The ATM p.Ile124= variant was not identified in the literature nor was it identified in the COGR, Cosmic, or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs773495195) as With Likely benign allele, and in ClinVar (classified as likely benign by Ambry Genetics, Invitae, Color Genomics). The variant was identified in control databases in 8 of 245932 chromosomes at a frequency of 0.000033 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: Latino in 1 of 33538 chromosomes (freq: 0.00003), European in 7 of 111506 chromosomes (freq: 0.0001); it was not observed in the African, Other, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Ile124Ile 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.
PreventionGenetics, part of Exact Sciences	RCV004552906	SCV004780102	likely benign	ATM-related disorder	2023-05-31	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).