ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4578C>T (p.Pro1526=) (rs1800889)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 21
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119133 SCV000153847 benign Ataxia-telangiectasia syndrome 2020-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162381 SCV000212691 benign Hereditary cancer-predisposing syndrome 2014-11-19 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.
PreventionGenetics,PreventionGenetics RCV000116426 SCV000301670 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000119133 SCV000367056 benign Ataxia-telangiectasia syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Health, Inc RCV000162381 SCV000537351 benign Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000116426 SCV000538366 benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000162381 SCV000679693 likely benign Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000119133 SCV000743728 benign Ataxia-telangiectasia syndrome 2014-10-10 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000116426 SCV000856495 benign not specified 2017-08-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283660 SCV001157006 benign none provided 2020-07-15 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000119133 SCV001750398 benign Ataxia-telangiectasia syndrome 2021-07-01 criteria provided, single submitter clinical testing
GeneDx RCV001705826 SCV001895577 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 11505391, 27599564)
Genetic Services Laboratory, University of Chicago RCV000116426 SCV000150351 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000119133 SCV000732992 benign Ataxia-telangiectasia syndrome no assertion criteria provided clinical testing
True Health Diagnostics RCV000162381 SCV000787866 likely benign Hereditary cancer-predisposing syndrome 2018-03-02 no assertion criteria provided clinical testing
Natera, Inc. RCV000119133 SCV001462148 benign Ataxia-telangiectasia syndrome 2019-08-26 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356512 SCV001551709 benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Pro1526= variant was identified in 520 of 9784 proband chromosomes (frequency: 0.05) from individuals or families with unselected multiple myeloma, breast cancer and was identified in 395 of 6700 control chromosomes (frequency: 0.059) from healthy individuals (Austen 2008, Concannon 2008, Petereit 2013, Stredrick 2006, Tommiska 2006). The variant was also identified in dbSNP (ID: rs rs1800889) as “other”, ClinVar (classified as benign by Invitae, Ambry Genetics, Prevention Genetics, Color Genomics; classified as likely benign by Illumina, GSLUOC), Cosmic (classified as neutral), LOVD 3.0 (does not affect function), databases. The variant was not identified in GeneInsight-COGR, MutDB, ATM-LOVD, databases. The variant was identified in control databases in 9064 (227 homozygous) of 277100 chromosomes at a frequency of 0.03 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%: European (Non-Finnish) in 6425 of 126614 chromosomes (freq: 0.051), Other in 212 of 6458 chromosomes (freq: 0.033), Latino in 1062 of 34414 chromosomes (freq: 0.031), European (Finnish) in 641 of 25788 chromosomes (freq: 0.025), Ashkenazi Jewish* in 131 of 10146 chromosomes (freq: 0.013), South Asian in 396 of 30782 chromosomes (freq: 0.013). The p.Pro1526Pro 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 2 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. In addition, few studies suggest the variant not associated with breast cancer risk and classify the variant as SNP (Stredrick 2006, Tommiska 2006). In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000116426 SCV001800467 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000116426 SCV001906001 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000116426 SCV001923647 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000116426 SCV001959229 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.