ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.998C>T (p.Ser333Phe) (rs28904919)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120169 SCV000149186 likely benign not specified 2017-12-11 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.
Invitae RCV000119232 SCV000153977 benign Ataxia-telangiectasia syndrome 2018-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115277 SCV000172886 likely benign Hereditary cancer-predisposing syndrome 2017-12-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000120169 SCV000602564 likely benign not specified 2016-12-09 criteria provided, single submitter clinical testing
Color RCV000115277 SCV000682544 likely benign Hereditary cancer-predisposing syndrome 2015-02-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586032 SCV000694395 likely benign not provided 2016-05-09 criteria provided, single submitter clinical testing Variant summary: ATM c.998C>T affects a conserved nucleotide, resulting in an amino acid change from Ser to Phe. 2/3 in-silico tools predict this variant to be damaging (SNPs&GO and MutationTaster not captured due to low reliability index).This variant was found in patients with MCL, idiopathic juxtafoveolar retinal telangiectasia, breast cancer, CLL, and CRC in germline and in tumor samples. However, co-segregation data were not available in these studies to establish causality of this variant in many studies. In one breast cancer family published in the literature, only the index patient had the variant while 3 affected sisters did not (Tommiska_2006), suggesting that this variant was not causative. The variant of interest was also found in 165/125148 control chromosomes at a frequency of 0.0013184. Specifically, in Finnish control population, MAF of this variant is 0.004548, which is greater than the estimated maximal expected frequency of a pathogenic ATM allele for AT (0.003953) or breast cancer (0.0005001), suggesting this variant is benign. In addition, multiple clinical laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant was classified as Likely Benign until additional information is available.
PreventionGenetics,PreventionGenetics RCV000586032 SCV000805637 likely benign not provided 2017-03-17 criteria provided, single submitter clinical testing
ITMI RCV000120169 SCV000084311 not provided not specified 2013-09-19 no assertion provided reference population

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