ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8104G>A (p.Ala2702Thr) (rs587779808)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000679088 SCV000149035 uncertain significance not provided 2014-01-06 criteria provided, single submitter clinical testing This variant is denoted APC c.8104G>A at the cDNA level, p.Ala2702Thr (A2702T) at the protein level, and results in the change of an Alanine to a Threonine (GCA>ACA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ala2702Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution in which a neutral non-polar amino acid is replaced with a neutral polar one, altering a position that is highly variable throughout evolution and is located in in the EB1 binding domain. In silico analyses predict this variant to have a benign effect on protein structure and function. Based on the currently available information, we consider APC Ala2702Thr to be a variant of uncertain significance.
Ambry Genetics RCV000115126 SCV000215279 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000646465 SCV000768237 uncertain significance Familial adenomatous polyposis 1 2018-07-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 2702 of the APC protein (p.Ala2702Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 127323). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics,PreventionGenetics RCV000679088 SCV000805477 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing

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