Submissions for variant NM_004655.4(AXIN2):c.1101C>T (p.Pro367=)

gnomAD frequency: 0.00094  dbSNP: rs141697521

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123793	SCV000167136	benign	not specified	2014-03-18	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.
Invitae	RCV000226243	SCV000288642	benign	Oligodontia-cancer predisposition syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000226243	SCV000405711	benign	Oligodontia-cancer predisposition syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000858430	SCV001151406	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	AXIN2: BP4, BP7
Ambry Genetics	RCV001017309	SCV001178375	likely benign	Hereditary cancer-predisposing syndrome	2018-11-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000123793	SCV001362149	benign	not specified	2019-02-25	criteria provided, single submitter	clinical testing	Variant summary: The variant, AXIN2 c.1101C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00078 in 276804 control chromosomes. The observed variant frequency is approximately 5 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.1101C>T in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign or likely benign. Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000858430	SCV002046812	benign	not provided	2021-04-02	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001017309	SCV002537569	benign	Hereditary cancer-predisposing syndrome	2020-11-25	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000123793	SCV002551286	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000226243	SCV004016312	benign	Oligodontia-cancer predisposition syndrome	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925230	SCV004740391	benign	AXIN2-related condition	2019-02-19	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).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000858430	SCV001808501	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000858430	SCV001918862	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000858430	SCV001972923	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000858430	SCV002036223	likely benign	not provided		no assertion criteria provided	clinical testing