Submissions for variant NM_000038.6(APC):c.4702GAT[3] (p.Asp1571del)

dbSNP: rs587782888

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000132525	SCV000187622	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-27	criteria provided, single submitter	clinical testing	The c.4711_4713delGAT variant (also known as p.D1571del) is located in coding exon 15 of the APC gene. This variant results from an in-frame GAT deletion at nucleotide positions 4711 to 4713. This results in the in-frame deletion of an aspartic acid at codon 1571. This amino acid position is highly 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.
GeneDx	RCV000480821	SCV000570617	uncertain significance	not provided	2019-04-30	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Variant located in the 20-aa repeat B-catenin down-regulating domain and the SAMP repeats/axin binding domain (Azzopardi 2008); This variant is associated with the following publications: (PMID: 25980754)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002514757	SCV000647534	uncertain significance	Familial adenomatous polyposis 1	2024-12-12	criteria provided, single submitter	clinical testing	This variant, c.4711_4713del, results in the deletion of 1 amino acid(s) of the APC protein (p.Asp1571del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587782888, gnomAD 0.003%). 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: 143006). 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.
Color Diagnostics, LLC DBA Color Health	RCV000132525	SCV000911472	likely benign	Hereditary cancer-predisposing syndrome	2017-01-17	criteria provided, single submitter	clinical testing
Mendelics	RCV002247511	SCV002516884	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002247511	SCV004024368	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV002514757	SCV004195815	uncertain significance	Familial adenomatous polyposis 1	2023-12-29	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000480821	SCV005624510	uncertain significance	not provided	2024-01-19	criteria provided, single submitter	clinical testing	The APC c.4711_4713del (p.Asp1571del) variant has been reported in the published literature in an individual affected with a Lynch syndrome associated cancer and/or polyps (PMID: 25980754 (2015)). The frequency of this variant in the general population, 0.000004 (1/250660 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.