Submissions for variant NM_004655.4(AXIN2):c.2282C>A (p.Ala761Asp)

gnomAD frequency: 0.00649  dbSNP: rs79732150

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212103	SCV000167149	benign	not specified	2013-10-11	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	RCV000123806	SCV000266996	likely benign	Hereditary cancer-predisposing syndrome	2016-01-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000225871	SCV000288699	benign	Oligodontia-cancer predisposition syndrome	2025-02-04	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212103	SCV000593564	likely benign	not specified	2016-08-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000212103	SCV000916642	benign	not specified	2018-04-06	criteria provided, single submitter	clinical testing	Variant summary: AXIN2 c.2282C>A (p.Ala761Asp) results in a non-conservative amino acid change located in the DIX domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0018 in 121402 control chromosomes. The observed variant frequency is approximately 13 fold of 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.2282C>A in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics	RCV000123806	SCV001175846	benign	Hereditary cancer-predisposing syndrome	2018-10-29	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212103	SCV002774035	benign	not specified	2021-08-26	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002505079	SCV002798514	likely benign	Oligodontia-cancer predisposition syndrome; Colorectal cancer	2021-10-24	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000225871	SCV004016313	benign	Oligodontia-cancer predisposition syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000212103	SCV000691771	benign	not specified		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530068	SCV004718431	benign	AXIN2-related disorder	2019-07-31	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).