ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1810C>T (p.Pro604Ser) (rs2227922)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000590282 SCV000602566 benign not provided 2017-06-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115147 SCV000172759 benign Hereditary cancer-predisposing syndrome 2014-06-19 criteria provided, single submitter clinical testing
Color RCV000115147 SCV000537384 benign Hereditary cancer-predisposing syndrome 2014-12-16 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000122824 SCV000745123 uncertain significance Ataxia-telangiectasia syndrome 2016-06-28 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000120119 SCV000225475 likely benign not specified 2015-09-15 criteria provided, single submitter clinical testing
GeneDx RCV000120119 SCV000149056 benign not specified 2017-05-26 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.
Genetic Services Laboratory, University of Chicago RCV000120119 SCV000246612 likely benign not specified 2015-08-03 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000122824 SCV000743721 likely benign Ataxia-telangiectasia syndrome 2015-06-16 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000122824 SCV000745807 likely benign Ataxia-telangiectasia syndrome 2016-07-11 no assertion criteria provided clinical testing
ITMI RCV000120119 SCV000084256 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000590282 SCV000694200 benign not provided 2016-05-09 criteria provided, single submitter clinical testing Variant summary: The ATM variant, c.1810C>T (p.Pro604Ser) causes a missense change involving a conserved nucleotide with 2/4 in silico programs (SNPs&GO not captured here due to low reliability index) predict a "benign" outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 345/111640 (1/323 including 5 homozygotes), which significantly exceeds the estimated maximum expected allele frequency for a pathogenic ATM variant of 1/2000 for Breast Cancer. Therefore, suggesting the variant is a common polymorphism. The variant of interest has been reported in multiple affected individuals via publications with varying phenotypes (BrC, Lynch syndrome, B-CLL, PrC, lymphoma, Hodgkin's disease), including one individual dx with A-T that harbored this variant and another ATM variant, c.6482G>C (p.Arg2161Pro - not yet scored) and was indicated to have absent ATM protein. Two internal LCA samples (adult patients with unknown phenotypes) carried c.1810C>T variant with another pathogenic variants: 1 with a BRIP1 variant, c.440dupA (Tyr147X - classified likely pathogenic) and 1 with an ATM variant, c.1027_1030delGAAA (p.Glu343fsX2 - classified pathogenic). In addition, multiple reputable clinical laboratories cite the variant with a classification of "likely benign/benign." Therefore, taking all available information into consideration for the phenotype of Breast Cancer, the variant of interest is classified as Benign.
Invitae RCV000122824 SCV000166081 benign Ataxia-telangiectasia syndrome 2018-01-15 criteria provided, single submitter clinical testing
Mendelics RCV000122824 SCV000838494 likely benign Ataxia-telangiectasia syndrome 2018-07-02 criteria provided, single submitter clinical testing
PreventionGenetics RCV000120119 SCV000805505 benign not specified 2016-11-21 criteria provided, single submitter clinical testing

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