Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165552 | SCV000216284 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-11-09 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |
| Color | RCV000165552 | SCV000292206 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-27 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000780910 | SCV000918552 | uncertain significance | not specified | 2018-07-13 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.4365T>A (p.Ser1455Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246182 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4365T>A has been reported in the literature in one individual affected with childhood Hodgkin disease. This report does not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia. One study reported the finding of defective ATM-mediated p53 phosphorylation and Chk2 activation in lymphoblastoid cell lines obtained from a patient with childhood Hodgkin disease harboring this variant. However these results cannot be specifically correlated to the pathophysiology and in-vivo effect of this variant as the results obtained could be attributed to another genetic variant unrelated to this specific variant. The authors presented their findings in the context of possible genetic risk factors for childhood Hodgkin disease. To our knowledge, no other direct experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (2 VUS and 1 likely benign). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV000232578 | SCV000282957 | likely benign | Ataxia-telangiectasia syndrome | 2017-12-27 | criteria provided, single submitter | clinical testing |