ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2193C>T (p.Tyr731=) (rs2229019)

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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 RCV000128878 SCV000172735 benign Hereditary cancer-predisposing syndrome 2014-11-25 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.
Invitae RCV000206183 SCV000262430 benign Ataxia-telangiectasia syndrome 2020-12-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000206183 SCV000367033 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 RCV000128878 SCV000682039 benign Hereditary cancer-predisposing syndrome 2015-04-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679102 SCV000805512 benign not specified 2015-09-14 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000710665 SCV000840924 benign not provided 2018-05-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285763 SCV001472244 benign none provided 2020-06-05 criteria provided, single submitter clinical testing
GeneDx RCV000710665 SCV001945465 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000128878 SCV000805211 likely benign Hereditary cancer-predisposing syndrome 2018-06-18 no assertion criteria provided clinical testing
Natera, Inc. RCV000206183 SCV001461022 benign Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354816 SCV001549522 benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Tyr731Tyr variant was identified in 3 of 712 proband chromosomes (frequency: 0.004) from individuals or families with breast cancer or leukemia (Mangone 2015, Gumy Pause 2003, Dörk 2001). The variant was also identified in dbSNP (ID: rs2229019) as "With other allele", in ClinVar (classified as 2x benign, 1x likely benign), Clinvitae (classified as 1x benign, 1x conflicting interpretations of pathogenicity), and Cosmic (1x as neutral). The variant was not identified in the MutDB, LOVD 3.0, or ATM-LOVD databases. The variant was identified in control databases in 1336 of 276956 (35 homozygous) chromosomes at a frequency of 0.005 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 1213 of 24022 chromosomes (freq: 0.05). The p.Tyr731Tyr 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 addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000679102 SCV001905922 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000679102 SCV001922173 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000679102 SCV001951867 benign not specified no assertion criteria provided clinical testing

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