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

dbSNP: rs587779808

Total submissions: 4

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	2021-08-18	criteria provided, single submitter	clinical testing	The p.A2702T variant (also known as c.8104G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 8104. The alanine at codon 2702 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV003743568	SCV000768237	uncertain significance	Familial adenomatous polyposis 1	2023-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2702 of the APC protein (p.Ala2702Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 127323). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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, part of Exact Sciences	RCV000679088	SCV000805477	uncertain significance	not provided	2017-06-01	criteria provided, single submitter	clinical testing