ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1744T>C (p.Phe582Leu) (rs2235006)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115146 SCV000183793 benign Hereditary cancer-predisposing syndrome 2014-11-24 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000588398 SCV000840921 likely benign not provided 2018-03-02 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000588398 SCV000892001 uncertain significance not provided 2018-09-30 criteria provided, single submitter clinical testing
Color RCV000115146 SCV000681996 likely benign Hereditary cancer-predisposing syndrome 2015-04-07 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000122822 SCV000745122 likely benign Ataxia-telangiectasia syndrome 2017-05-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000120118 SCV000225147 likely benign not specified 2015-03-20 criteria provided, single submitter clinical testing
GeneDx RCV000120118 SCV000149055 benign not specified 2017-06-08 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.
Genetic Services Laboratory, University of Chicago RCV000120118 SCV000593498 likely benign not specified 2017-01-27 criteria provided, single submitter clinical testing
ITMI RCV000120118 SCV000084255 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000588398 SCV000694196 likely benign not provided 2017-05-22 criteria provided, single submitter clinical testing Variant summary: Variant affects a non-conserved nucleotide and results in a replacement of a large size and aromatic Phenylalanine (F) with a medium size and hydrophobic Leucine (L). 4/4 in silico tools predict the variant to be neutral. It was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.098% which does not exceed the maximal expected allele frequency of a disease causing AT allele (0.4%). The variant was reported in CLL, ALL and breast cancer patients, however without information about family history and co-segregation, therefore these reports do not provide strong evidence for a casual impact of the variant. It was reported as a germline alteration in a patient with T-ALL associated with a t(11:14) translocation by cytogenetic analysis with no evidence of an allelic loss in tumor DNA. One publication suggest the variant to confer a risk for CLL (OR:11.23) based on a case control study, however, the significance of this finding is uncertain due to the OR being calculated based on only one affected patient (Rudd_Blood_2006). In other studies, reporting an OR for association with sporadic T-ALL, the 95% CI's overlapped 1.0, and had very small sample sizes, thereby providing little to no confidence in the assertion of the assertion. On study reported the variant to result in normal ATM protein levels, normal kinase activity, and corrected radiosensitivity when expressed in A-T cells indicating neutrality. At least three publications (Mitui_Hum Mut_2009, Magliozzi_DiseaseMarkers_2006, Maxwell_AJHG_2016) and several clinical diagnostic laboratories classify this variant as Benign/Likely Benign. Considering all evidence, the variant was classified as Likely Benign until more information becomes available.
Invitae RCV000122822 SCV000166079 benign Ataxia-telangiectasia syndrome 2018-01-03 criteria provided, single submitter clinical testing
PreventionGenetics RCV000120118 SCV000301655 likely benign not specified criteria provided, single submitter clinical testing
PreventionGenetics RCV000588398 SCV000805504 likely benign not provided 2016-03-17 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000115146 SCV000787847 likely benign Hereditary cancer-predisposing syndrome 2018-02-20 no assertion criteria provided clinical testing

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