ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6184A>G (p.Lys2062Glu)

dbSNP: rs1561605668
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001191757 SCV001359656 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-22 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamic acid at codon 2062 of the APC protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV004570401 SCV002257757 uncertain significance Familial adenomatous polyposis 1 2022-05-13 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 928102). 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 lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 2062 of the APC protein (p.Lys2062Glu).
Ambry Genetics RCV001191757 SCV005459915 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-04 criteria provided, single submitter clinical testing The p.K2062E variant (also known as c.6184A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 6184. The lysine at codon 2062 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear.

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