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
Invitae	RCV000225871	SCV000288699	benign	Oligodontia-cancer predisposition syndrome	2024-02-01	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: 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
PreventionGenetics, part of Exact Sciences	RCV003905190	SCV004718431	benign	AXIN2-related condition	2019-07-31	criteria provided, single submitter	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).
Mayo Clinic Laboratories, Mayo Clinic	RCV000212103	SCV000691771	benign	not specified		no assertion criteria provided	clinical testing