ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.5975A>C (p.Lys1992Thr) (rs150757822)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115220 SCV000172870 likely benign Hereditary cancer-predisposing syndrome 2017-05-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign),Subpopulation frequency in support of benign classification,Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Athena Diagnostics Inc RCV000588284 SCV000840947 benign not provided 2018-08-03 criteria provided, single submitter clinical testing
Color RCV000115220 SCV000902598 likely benign Hereditary cancer-predisposing syndrome 2016-05-18 criteria provided, single submitter clinical testing
Counsyl RCV000122863 SCV000799792 uncertain significance Ataxia-telangiectasia syndrome 2018-05-10 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515391 SCV000611369 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2017-05-23 criteria provided, single submitter clinical testing
GeneDx RCV000212036 SCV000149129 likely benign not specified 2018-02-08 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.
GeneKor MSA RCV000115220 SCV000821864 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212036 SCV000694313 likely benign not specified 2018-10-01 criteria provided, single submitter clinical testing Variant summary: ATM c.5975A>C (p.Lys1992Thr) results in a non-conservative amino acid change located in the PIK-related kinase, FAT domain (IPR003151) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 297344 control chromosomes (gnomAD, FLOSSIES and publication data), predominantly observed within the Ashkenazi Jewish subpopulation at a frequency of 0.0044 in the gnomAD database, including 1 homozygote. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Ataxia-Telangiectasia phenotype (0.004), suggesting that the variant might be a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. The variant, c.5975A>C, has been reported in the literature in individuals with breast cancer, chronic lymphocytic leukemia, and pancreatic ductal adenocarcinoma, however, without clear evidence supporting pathogenicity (Bernstein_2010, Skowronska_2011, Navrkalova_2013, Young_2016, Zhang_2015, Tung_2014, Shindo_2017, Tiao_2017). Seven other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign x4, VUS x3). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000122863 SCV000166121 likely benign Ataxia-telangiectasia syndrome 2018-01-12 criteria provided, single submitter clinical testing
Mendelics RCV000122863 SCV000838564 uncertain significance Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000588284 SCV000805590 uncertain significance not provided 2017-11-10 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000115220 SCV000805218 likely benign Hereditary cancer-predisposing syndrome 2018-05-03 no assertion criteria provided clinical testing

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