ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6278C>T (p.Ser2093Phe)

gnomAD frequency: 0.00001  dbSNP: rs879254172
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236754 SCV000293707 uncertain significance not provided 2015-12-16 criteria provided, single submitter clinical testing This variant is denoted APC c.6278C>T at the cDNA level, p.Ser2093Phe (S2093F) at the protein level, and results in the change of a Serine to a Phenylalanine (TCC>TTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Ser2093Phe was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Phenylalanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. APC Ser2093Phe occurs at a position that is conserved across species and is not located in a known functional domain (Azzopardi 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether APC Ser2093Phe is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV003535659 SCV000647633 uncertain significance Familial adenomatous polyposis 1 2023-07-25 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 246238). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2093 of the APC protein (p.Ser2093Phe).
Ambry Genetics RCV002365228 SCV002660882 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-29 criteria provided, single submitter clinical testing The p.S2093F variant (also known as c.6278C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 6278. The serine at codon 2093 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.