Submissions for variant NM_000051.4(ATM):c.8532T>C (p.Ile2844=)

gnomAD frequency: 0.00001  dbSNP: rs730881278

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212085	SCV000209581	benign	not specified	2014-06-26	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	RCV000159598	SCV000215925	likely benign	Hereditary cancer-predisposing syndrome	2014-08-04	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	RCV000231198	SCV000283085	benign	Ataxia-telangiectasia syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000159598	SCV000687839	likely benign	Hereditary cancer-predisposing syndrome	2017-02-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000212085	SCV000916560	likely benign	not specified	2019-08-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000231198	SCV001264111	uncertain significance	Ataxia-telangiectasia syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sema4, Sema4	RCV000159598	SCV002529890	likely benign	Hereditary cancer-predisposing syndrome	2022-03-05	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212085	SCV004024611	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004589652	SCV005083696	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.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000159598	SCV005415575	likely benign	Hereditary cancer-predisposing syndrome	2024-09-16	criteria provided, single submitter	clinical testing	The synonymous variant NM_000051.4(ATM):c.8532T>C (p.Ile2844=) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ile2844= variant is observed in 6/113,572 (0.0053%) alleles from individuals of gnomAD Non Finnish European background in gnomAD. The p.Ile2844= variant is predicted to introduce a novel splice site by 1 of 4 splice site algorithms. The p.Ile2844= variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Likely Benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580007	SCV001809342	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001580007	SCV001953375	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004551365	SCV004766124	likely benign	ATM-related disorder	2019-12-17	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).