Submissions for variant NM_004655.4(AXIN2):c.2272G>A (p.Ala758Thr)

gnomAD frequency: 0.00179  dbSNP: rs145007501

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000586946	SCV000149784	likely benign	not provided	2021-03-01	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26406231, 21626677, 24581859, 25186949, 27090353, 25801821, 27365112, 29371908, 29772684)
Invitae	RCV000205073	SCV000261931	benign	Oligodontia-cancer predisposition syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Vantari Genetics	RCV000115875	SCV000266997	uncertain significance	Hereditary cancer-predisposing syndrome	2016-02-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000205073	SCV000405679	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). No publications were found based on this search. Allele frequency data from public databases allowed determination 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	RCV000586946	SCV000698520	likely benign	not provided	2016-08-17	criteria provided, single submitter	clinical testing	Variant summary: The AXIN2 c.2272G>A (p.Ala758Thr) variant causes a missense change involving a non-conserved nucleotide with 3/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 291/121600 (1/417), which exceeds the estimated maximal expected allele frequency for a pathogenic AXIN2 variant of 1/7037, suggesting this variant is likely a benign polymorphism. The variant of interest has been reported in an affected individual with tooth agenesis, but had no family history of colorectal cancer. However, tooth agenesis has been implicated as a precursor for cancer, although this cannot be established for the current variant due to limited available information. Multiple clinical laboratories cite the variant with conflicting classifications "uncertain significance" or "likely benign." Therefore, until additional information becomes available the variant of interest has been classified as Likely Benign.
Ambry Genetics	RCV000115875	SCV001175793	likely benign	Hereditary cancer-predisposing syndrome	2019-11-21	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000586946	SCV001473768	likely benign	not provided	2023-11-03	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000586946	SCV002009783	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212102	SCV002069068	benign	not specified	2021-06-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000115875	SCV002537167	likely benign	Hereditary cancer-predisposing syndrome	2021-07-30	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212102	SCV002551230	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212102	SCV002773957	benign	not specified	2021-10-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586946	SCV004138831	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	AXIN2: BP4, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003935107	SCV004749459	likely benign	AXIN2-related condition	2019-10-25	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
CSER _CC_NCGL, University of Washington	RCV000417339	SCV000503519	likely benign	Oligodontia; Colorectal cancer	2016-08-01	no assertion criteria provided	research	Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 19 year old with a history of a tubulovillous adenoma at age 16.
Mayo Clinic Laboratories, Mayo Clinic	RCV000212102	SCV000691772	uncertain significance	not specified		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000586946	SCV000840120	not provided	not provided		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000586946	SCV001970538	likely benign	not provided		no assertion criteria provided	clinical testing