ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1953A>G (p.Leu651=) (rs730881283)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000211970 SCV000209589 benign not specified 2014-09-23 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 RCV000159605 SCV000214867 likely benign Hereditary cancer-predisposing syndrome 2014-08-01 criteria provided, single submitter clinical testing This alteration is classified as likely 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 RCV001079832 SCV000558341 likely benign Ataxia-telangiectasia syndrome 2020-11-26 criteria provided, single submitter clinical testing
Color Health, Inc RCV000159605 SCV000682016 likely benign Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000211970 SCV000694204 likely benign not specified 2021-01-15 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000587703 SCV000805510 likely benign not provided 2017-01-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000587703 SCV001551243 likely benign not provided no assertion criteria provided clinical testing The ATM p.Leu651= variant was identified in 14 of 14208 proband chromosomes (frequency: 0.001) from Japanese individuals or families with breast cancer and was present in 43 of 47462 control chromosomes (frequency: 0.0009) from healthy individuals (Momozawa 2018). The variant was also identified in dbSNP (ID: rs730881283) “With Uncertain significance allele”, ClinVar (classified as benign by GeneDx; as likely benign by Ambry Genetics, Invitae, Color, and Prevention Genetics; and as uncertain significance by Integrated Genetics/Laboratory Corporation of America), and LOVD 3.0 (1x as benign). The variant was identified in control databases in 22 of 277048 chromosomes at a frequency of 0.00008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 24030 chromosomes (freq: 0.00004), Other in 1 of 6460 chromosomes (freq: 0.0002), Latino in 14 of 34416 chromosomes (freq: 0.0004), European Non-Finnish in 5 of 126592 chromosomes (freq: 0.00004), and South Asian in 1 of 30778 chromosomes (freq: 0.00003), while not observed in the Ashkenazi Jewish, East Asian, or European Finnish populations. The p.Leu651= 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) do not predict a difference in splicing. 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.

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