Submissions for variant NM_004655.4(AXIN2):c.1573C>G (p.Pro525Ala)

gnomAD frequency: 0.00930  dbSNP: rs73346297

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123800	SCV000167143	benign	not specified	2013-12-02	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000461945	SCV000559497	benign	Oligodontia-cancer predisposition syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001012214	SCV001172640	benign	Hereditary cancer-predisposing syndrome	2018-09-20	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000123800	SCV001362151	benign	not specified	2019-01-15	criteria provided, single submitter	clinical testing	Variant summary: AXIN2 c.1573C>G (p.Pro525Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0026 in 277090 control chromosomes in the gnomAD database, including 14 homozygotes. The observed variant frequency is approximately 19-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in AXIN2 causing Colorectal Cancer phenotype (0.00014), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1573C>G in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001800413	SCV001474092	benign	not provided	2019-10-11	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000123800	SCV002046724	benign	not specified	2021-03-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000123800	SCV002069090	benign	not specified	2021-04-02	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000461945	SCV004016320	benign	Oligodontia-cancer predisposition syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000123800	SCV004242920	benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001800413	SCV005255547	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000123800	SCV000691783	likely benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530067	SCV004736893	benign	AXIN2-related disorder	2019-07-18	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).