ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1254A>G (p.Gln418=) (rs4987943)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 15
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119159 SCV000153880 benign Ataxia-telangiectasia syndrome 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130976 SCV000185893 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.
Illumina Clinical Services Laboratory,Illumina RCV000119159 SCV000367027 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282653 SCV000602554 benign none provided 2020-06-05 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000130976 SCV000679695 likely benign Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130976 SCV000681962 benign Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000506744 SCV000805493 benign not specified 2016-11-02 criteria provided, single submitter clinical testing
GeneDx RCV001705878 SCV001889119 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 17333338)
True Health Diagnostics RCV000130976 SCV000787843 likely benign Hereditary cancer-predisposing syndrome 2018-01-03 no assertion criteria provided clinical testing
Natera, Inc. RCV000119159 SCV001456887 benign Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357804 SCV001553388 benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM, p.Gln418= variant was identified in 7 of 580 proband chromosomes (frequency: 0.01) from African-American, Caucasian, and Egyptian individuals or families with breast cancer or acute lymphoblastic leukemia and was present in 18 of 884 control chromosomes (frequency: 0.02) from healthy individuals (Rosenstein 2006, Meier 2005, Kim 2017). The variant was identified in dbSBP (ID: rs4987943) as "With other allele", ClinVar database (classified as benign by Invitae and Ambry Genetics; and likely benign by Illumina), Clinvitae (2x), and LOVD 3.0 (effect unknown) databases; and was not identified in the COSMIC, MutDB or LOVD-ATM databases. The variant was identified in control databases in 2296 of 271418 chromosomes (80 homozygous) at a frequency of 0.008 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 1912 of 23758 chromosomes (freq: 0.08). The c.1254A>G 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 p.Gln418= 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 summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000506744 SCV001807520 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000506744 SCV001906410 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000506744 SCV001924622 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000506744 SCV001952345 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.