ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2119T>C (p.Ser707Pro) (rs4986761)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 24
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000116422 SCV000150347 benign not specified 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000119131 SCV000153845 benign Ataxia-telangiectasia syndrome 2020-12-05 criteria provided, single submitter clinical testing
GeneDx RCV000116422 SCV000167069 benign not specified 2013-09-04 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 RCV000128903 SCV000172764 benign Hereditary cancer-predisposing syndrome 2014-07-14 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000116422 SCV000225743 benign not specified 2015-02-26 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128903 SCV000292112 benign Hereditary cancer-predisposing syndrome 2014-12-04 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000116422 SCV000296849 benign not specified 2015-10-11 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283571 SCV000602556 benign none provided 2020-08-25 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000128903 SCV000679689 likely benign Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000119131 SCV000743722 likely benign Ataxia-telangiectasia syndrome 2014-10-09 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000119131 SCV000745808 likely benign Ataxia-telangiectasia syndrome 2015-11-08 criteria provided, single submitter clinical testing
Counsyl RCV000119131 SCV000789947 likely benign Ataxia-telangiectasia syndrome 2017-02-28 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000116422 SCV000805511 benign not specified 2016-10-10 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000710664 SCV000840922 benign not provided 2017-08-11 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000710664 SCV001148408 likely benign not provided 2020-07-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000119131 SCV001260415 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.
ITMI RCV000116422 SCV000084257 not provided not specified 2013-09-19 no assertion provided reference population
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000119131 SCV000732990 benign Ataxia-telangiectasia syndrome no assertion criteria provided clinical testing
True Health Diagnostics RCV000128903 SCV000787849 likely benign Hereditary cancer-predisposing syndrome 2018-01-12 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000710664 SCV001553525 likely benign not provided no assertion criteria provided clinical testing The ATM p.Ser707Pro variant was identified in 542 of 44368 proband chromosomes (frequency: 0.0122) from individuals or families with breast and thyroid cancer and was present in 6 of 1000 control chromosomes (frequency: 0.006) from healthy individuals (Dork 2001, Barbazetto 2008, Dombernowsky 2008, Fletcher 2010, Petereit 2013, Spurdle 2002). The variant was also identified in dbSNP (ID: rs4986761) as other, ClinVar (classified as benign by GeneDx, Ambry genetics, Emory genetics, Color Genomics, Invitae), Cosmic (classified as neutral), MutDB (classified as polymorphism), and LOVD 3.0 databases. The variant was not identified in GeneInsight-COGR and ATM-LOVD databases. The variant was identified in control databases in 2208 of 276136 chromosomes at a frequency of 0.007996 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) (6 homozygous) in 1508 of 126110 chromosomes (freq: 0.012), Other in 70 of 6438 chromosomes (freq: 0.011). In one study, the p.Ser707Pro variant appeared to be associated with high-risk breast carcinoma, characterized by a positive axillary nodal status and an increased risk of contralateral breast cancer (Dork, 2001). The p.Ser707Pro variant is likely to interfere with secondary and tertiary protein structure, as the exchange of proline for serine introduces a much bulkier side chain and removes a hydroxyl group that possibly participates in hydrogen bonding (Dork, 2001). However, several large population studies have shown that the variant was not associated with an increased breast cancer risk compared with the general population, or overall cancer risk (Barbazetto 2008, Choi 2016, Fletcher 2010, Spurdle 2002). In addition, in their study Thorstenson (2003) found the variant did not segregate with disease. The p.Ser707Pro residue is not conserved in mammals and mammals and the variant amino acid Proline (Pro) is present in several lower organisms, increasing the likelihood that this variant does not have clinical significance. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant is located with the Armadillo-type fold functional domain(s), the clinical significance of which cannot be determined. 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000710664 SCV001799432 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000710664 SCV001906415 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000116422 SCV001918055 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000116422 SCV001956738 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.