ClinVar Miner

Submissions for variant NM_000038.6(APC):c.6218G>A (p.Gly2073Asp)

dbSNP: rs1766164614
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001183855 SCV001349697 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 2073 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 APC-related disorders 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 RCV004570367 SCV001380813 uncertain significance Familial adenomatous polyposis 1 2023-12-18 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2073 of the APC protein (p.Gly2073Asp). 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: 923281). 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.
Ambry Genetics RCV001183855 SCV002655370 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-14 criteria provided, single submitter clinical testing The p.G2073D variant (also known as c.6218G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 6218. The glycine at codon 2073 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is well 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.
Fulgent Genetics, Fulgent Genetics RCV002484003 SCV002777745 uncertain significance Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach 2022-02-25 criteria provided, single submitter clinical testing

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