Submissions for variant NM_000038.6(APC):c.5102_5104del (p.Gln1701_Gly1702delinsArg)

gnomAD frequency: 0.00001  dbSNP: rs1554086446

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000579858	SCV000681707	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-27	criteria provided, single submitter	clinical testing	This variant causes a deletion of three nucleotides located in exon 16 of the APC gene, replacing two amino acids Glutamine and Glycine with an Arginine. 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	RCV004562529	SCV002196440	uncertain significance	Familial adenomatous polyposis 1	2024-09-23	criteria provided, single submitter	clinical testing	This variant, c.5102_5104del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the APC protein (p.Gln1701_Gly1702delinsArg). 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: 489464). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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	RCV000579858	SCV002645813	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-29	criteria provided, single submitter	clinical testing	The c.5102_5104delAAG variant (also known as p.Q1701_G1702delinsR) is located in coding exon 15 of the APC gene. This variant results from an in-frame AAG deletion at nucleotide positions 5102 to 5104. The amino acids at codons 1701 and 1702 are deleted and replaced by an arginine. These amino acid positions are not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV004001228	SCV004838003	uncertain significance	Classic or attenuated familial adenomatous polyposis	2024-02-05	criteria provided, single submitter	clinical testing	This variant causes a deletion of three nucleotides located in exon 16 of the APC gene, replacing two amino acids Glutamine and Glycine with an Arginine. 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.
GeneDx	RCV004722950	SCV005334314	uncertain significance	not provided	2023-12-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of two amino acids and the insertion of one in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528)