ClinVar Miner

Submissions for variant NM_000038.6(APC):c.7528A>G (p.Asn2510Asp)

dbSNP: rs730881263
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159574 SCV000209550 uncertain significance not provided 2014-05-23 criteria provided, single submitter clinical testing This variant is denoted APC c.7528A>G at the cDNA level, p.Asn2510Asp (N2510D) at the protein level, and results in the change of an Asparagine to an Aspartic Acid (AAT>GAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Asn2510Asp 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. Since Asparagine and Aspartic Acid differ in some properties, this is considered a semi-conservative amino acid substitution. APC Asn2510Asp occurs at a position that is highly conserved through mammals and is not located in a known functional domain. In addition, in silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether APC Asn2510Asp is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV003765005 SCV002248131 uncertain significance Familial adenomatous polyposis 1 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 2510 of the APC protein (p.Asn2510Asp). 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: 181822). 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 with a negative predictive value of 95%. 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.

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