Submissions for variant NM_004655.4(AXIN2):c.1615G>A (p.Val539Met)

gnomAD frequency: 0.01361  dbSNP: rs9913621

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212101	SCV000167144	benign	not specified	2013-10-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Vantari Genetics	RCV000123801	SCV000266998	benign	Hereditary cancer-predisposing syndrome	2015-12-01	criteria provided, single submitter	clinical testing
Invitae	RCV000232669	SCV000288667	benign	Oligodontia-cancer predisposition syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000232669	SCV000405691	likely benign	Oligodontia-cancer predisposition syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587784	SCV000698515	benign	not provided	2016-04-28	criteria provided, single submitter	clinical testing	Variant summary: The c.1615G>A variant affects a conserved nucleotide, resulting in amino acid change from Val to Met. 2/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant is found in 491/121392 control chromosomes (14 homozygotes) at a frequency of 0.0040447, which is about 28 times of the maximal expected frequency of a pathogenic allele (0.0001421). Variant is predominalty observed in African subpopulation in ExAC with MAF of 0.0434365, suggesting this variant is benign especially in Africans. In addition, multiple clinical laboratories classified this variant as benign. Taken together, this variant was classified as benign.
Ambry Genetics	RCV000123801	SCV001172874	benign	Hereditary cancer-predisposing syndrome	2019-05-08	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587784	SCV001472922	benign	not provided	2022-10-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212101	SCV002047218	benign	not specified	2021-06-08	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212101	SCV002551261	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477326	SCV002801788	benign	Oligodontia-cancer predisposition syndrome; Colorectal cancer	2021-12-22	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000232669	SCV004016302	benign	Oligodontia-cancer predisposition syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000212101	SCV000691782	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000212101	SCV001809503	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000212101	SCV001917282	benign	not specified		no assertion criteria provided	clinical testing