ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.657T>C (p.Cys219=) (rs2235003)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129174 SCV000183907 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.
Invitae RCV000206853 SCV000262252 benign Ataxia-telangiectasia syndrome 2020-12-06 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000116429 SCV000301682 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000206853 SCV000367022 benign Ataxia-telangiectasia syndrome 2018-01-12 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 RCV000129174 SCV000537402 benign Hereditary cancer-predisposing syndrome 2015-04-08 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000710677 SCV000840953 benign not provided 2017-11-10 criteria provided, single submitter clinical testing
GeneDx RCV000710677 SCV001900473 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000116429 SCV000150354 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.
True Health Diagnostics RCV000129174 SCV000787877 likely benign Hereditary cancer-predisposing syndrome 2017-09-11 no assertion criteria provided clinical testing
Natera, Inc. RCV000206853 SCV001454840 benign Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357712 SCV001553261 benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Cys219= variant was identified in 1 of 404 proband chromosomes (frequency: 0.0024) from individuals or families with cancer, although the cancer type was unspecified (Petereit 2013). The variant was also identified in 4 of 186 control chromsomes (freq. 0.022) in unaffected individuals (Thorstenson 2001). The variant was also identified in dbSBP (ID: rs2235003) as “With other allele,” ClinVar (as likely benign by Genetics Services Laboratory University of Chicago and Illumina and as benign by Ambry Genetics, Invitae, Prevention Genetics, and Color Genomics), Clinvitae, and ATM-LOVD databases. The variant was not identified in Cosmic, MutDB, LOVD 3.0 databases. The variant was identified in control databases in 2436 of 276942 chromosomes at a frequency of 0.008796 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the African population at a frequency greater than 1% in 2217 (101 homozygous) of 23994 chromosomes (freq: 0.092), and at lower frequencies in the following populations: Other in 22 of 6448 chromosomes (freq. 0.003), Latino in 166 (1 homozygous) of 34366 chromosomes (freq. 0.0048), and European (Non-Finnish) in 25 of 126568 chromosomes (freq. 0.0002), increasing the likelihood this could be a low frequency benign variant. The p.Cys219Cys 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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000116429 SCV001808539 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000116429 SCV001906265 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000116429 SCV001919766 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000116429 SCV001956851 benign not specified no assertion criteria provided clinical testing

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