ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4473C>T (p.Phe1491=) (rs4988008)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122850 SCV000166108 benign Ataxia-telangiectasia syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000212018 SCV000167091 benign not specified 2013-12-24 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 RCV000123748 SCV000212881 likely benign Hereditary cancer-predisposing syndrome 2016-11-10 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV000122850 SCV000367055 uncertain significance 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Color Health, Inc RCV000123748 SCV000682210 benign Hereditary cancer-predisposing syndrome 2015-04-10 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587530 SCV000694284 benign not provided 2016-03-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000212018 SCV000701957 benign not specified 2016-10-24 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000122850 SCV000745126 likely benign Ataxia-telangiectasia syndrome 2017-06-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000122850 SCV000745815 likely benign Ataxia-telangiectasia syndrome 2017-03-23 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000587530 SCV000805566 likely benign not provided 2017-05-15 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000587530 SCV000840942 benign not provided 2019-02-12 criteria provided, single submitter clinical testing
Mendelics RCV000122850 SCV001138503 likely benign Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000587530 SCV001148424 likely benign not provided 2021-06-01 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000123748 SCV000886663 likely benign Hereditary cancer-predisposing syndrome 2018-09-06 no assertion criteria provided clinical testing
Natera, Inc. RCV000122850 SCV001462146 likely benign Ataxia-telangiectasia syndrome 2020-01-05 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354679 SCV001549355 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Phe1491= variant was identified in 1 of 1010 proband chromosomes (frequency: 0.001) from individuals or families with prostate cancer, breast cancer or chronic lymphocytic leukemia, and was present in 6 of 1439 control chromosomes (freq. 0.004) from healthy individuals (Skowronska_2011_21933854, Stock_2013_NA, Rosentein_2006_NA). The variant was also identified in dbSNP (ID: rs4988008) as “With other allele”, Clinvar and Clinvitae (3x classified as benign by Invitae, GeneDx, Color Genomics; 1x classified as likely benign by Ambry Genetics; 1x classified as uncertain significance by Illumina), COSMIC (1x in acute myeloid leukemia, somatic status unconfirmed), and LOVD 3.0 (2 entries, not classified) databases. The variant was not identified in the GeneInsight-COGR or MutDB databases. The variant was identified in control databases in 333 of 277018 chromosomes (0 homozygous) at a frequency of 0.001 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 6 of 24020 chromosomes (freq: 0.0002), Other in 9 of 6456 chromosomes (freq: 0.001), Latino in 21 of 34412 chromosomes (freq: 0.0006), European Non-Finnish in 262 of 126558 chromosomes (freq: 0.002), Ashkenazi Jewish in 22 of 10150 chromosomes (freq: 0.002), European Finnish in 13 of 25778 chromosomes (freq: 0.0005) while the variant was not observed in the East Asian and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational predictions software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The p.Phe1491= 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 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 RCV000587530 SCV001906187 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000587530 SCV001917746 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000587530 SCV001927759 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000587530 SCV001956308 likely benign not provided no assertion criteria provided clinical testing

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