ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6071A>G (p.Asn2024Ser) (rs863224546)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196363 SCV000254028 uncertain significance Familial adenomatous polyposis 1 2015-05-27 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 2024 of the APC protein (p.Asn2024Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. 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 disruptive, but these predictions have not been confirmed by published functional studies. This variant has not been published in the literature and is not present in population databases. In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000236544 SCV000293403 uncertain significance not provided 2015-11-12 criteria provided, single submitter clinical testing This variant is denoted APC c.6071A>G at the cDNA level, p.Asn2024Ser (N2024S) at the protein level, and results in the change of an Asparagine to a Serine (AAC>AGC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Asn2024Ser 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 Asparagine and Serine share similar properties, this is considered a conservative amino acid substitution. APC Asn2024Ser occurs at a position that is conserved across species and is located in a Beta-catenin down-regulating domain as well as the SAMP repeats/axin binding 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 Asn2024Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.

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