ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3383A>G (p.Gln1128Arg) (rs2229020)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000224651 SCV000167082 benign not provided 2019-01-16 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 17333338, 20981092, 22529920, 11996792, 24728327, 25122203, 22071889, 21933854)
Ambry Genetics RCV000128988 SCV000172879 benign Hereditary cancer-predisposing syndrome 2014-11-20 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
Invitae RCV000204666 SCV000261654 benign Ataxia-telangiectasia syndrome 2020-11-27 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224651 SCV000281587 likely benign not provided 2016-04-28 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120133 SCV000339808 benign not specified 2016-02-29 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000128988 SCV000576460 likely benign Hereditary cancer-predisposing syndrome 2017-02-14 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128988 SCV000682125 benign Hereditary cancer-predisposing syndrome 2015-03-05 criteria provided, single submitter clinical testing
Counsyl RCV000204666 SCV000799196 likely benign Ataxia-telangiectasia syndrome 2018-04-11 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120133 SCV000805539 benign not specified 2016-12-12 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000204666 SCV001260526 likely benign 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287273 SCV001473948 benign none provided 2020-02-18 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000120133 SCV001474792 benign not specified 2020-06-08 criteria provided, single submitter clinical testing
ITMI RCV000120133 SCV000084272 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV000204666 SCV001462134 benign Ataxia-telangiectasia syndrome 2020-04-17 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356319 SCV001551453 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Gln1128Arg variant was identified in 8 of 9204 proband chromosomes (frequency: 0.000869) from individuals or families with breast cancer, CLL, Ataxia telangiectasia and was present in 2 of 5218 control chromosomes (frequency: 0.0003) from healthy individuals (Austen 2005, Jacquemin 2011, Skowronska 2012, Tavtigian 2009). The variant was also identified in dbSNP (ID: rs2229020) as With other allele, ClinVar (classified as benign by GenDx, Ambry Genetics, Invitae), Clinvitae (classified as benign by ClinVar, Invitae), Cosmic (pathogenic), MutDB, databases. The variant was not identified in LOVD 3.0, ATM-LOVD, databases. The variant was identified in control databases in 601(8 homozygous) of 276616 chromosomes at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 528 of 24022 chromosomes (freq: 0.022). The p.Gln1128 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. The variant is located with the Armadillo-type fold functional domain increasing the likelihood that it may have clinical significance. 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.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120133 SCV001906360 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120133 SCV001957493 benign not specified no assertion criteria provided clinical testing

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