ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6566A>G (p.Lys2189Arg)

dbSNP: rs986763235
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001025414 SCV001187597 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-07 criteria provided, single submitter clinical testing The p.K2189R variant (also known as c.6566A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 6566. The lysine at codon 2189 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health RCV001025414 SCV002053626 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-13 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 2189 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/249068 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV001025414 SCV002528798 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-02 criteria provided, single submitter curation
Invitae RCV003744715 SCV003330501 uncertain significance Familial adenomatous polyposis 1 2023-10-25 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2189 of the APC protein (p.Lys2189Arg). 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: 826485). 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.
Baylor Genetics RCV002552396 SCV004197597 uncertain significance Familial adenomatous polyposis 1 2023-10-27 criteria provided, single submitter clinical testing

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