Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220698 | SCV000275426 | likely benign | Hereditary cancer-predisposing syndrome | 2015-04-23 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000507103 | SCV000600063 | likely benign | not specified | 2017-01-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000530592 | SCV000647267 | likely benign | Familial adenomatous polyposis 1 | 2017-12-14 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000507103 | SCV000728926 | likely benign | not specified | 2017-06-21 | 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. |
Color | RCV000220698 | SCV000904122 | likely benign | Hereditary cancer-predisposing syndrome | 2018-02-05 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000507103 | SCV000916508 | likely benign | not specified | 2018-10-01 | criteria provided, single submitter | clinical testing | Variant summary: APC c.2778T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.9e-05 in 276802 control chromosomes and was observed exclusively in the African subpopulation of the gnomAD database at a frequency of 0.00033. This frequency is approximately 5-fold above the maximal expected allele frequency for a pathogenic variant in Familial Adenomatous Polyposis, suggesting the variant is a benign polymorphism found in populations of African ancestry. To our knowledge, no occurrence of c.2778T>C in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |