Submissions for variant NM_004655.4(AXIN2):c.2285G>A (p.Ser762Asn)

gnomAD frequency: 0.00064  dbSNP: rs117688560

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000656577	SCV000149785	likely benign	not provided	2021-05-06	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24631698, 25236910, 15841489, 29114927)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206733	SCV000262295	benign	Oligodontia-cancer predisposition syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000206733	SCV000405678	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.
Ambry Genetics	RCV001015062	SCV001175855	likely benign	Hereditary cancer-predisposing syndrome	2022-11-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV002228347	SCV002046991	benign	not specified	2021-04-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000656577	SCV002048481	uncertain significance	not provided	2020-11-10	criteria provided, single submitter	clinical testing	The AXIN2 c.2285G>A; p.Ser762Asn variant (rs117688560), to our knowledge, is not reported as a germline variant in an individual with hereditary cancer, but has been reported as a somatic variant in a hepatoblastoma (Mazzoni 2014). The variant is reported in the ClinVar database (Variation ID: 127944) and is found in the general population with an overall allele frequency of 0.07% (196/282,902 alleles, including 1 homozygote) in the Genome Aggregation Database. The serine at codon 762 is moderately conserved and computational analyses predict that this variant is neutral (REVEL 0.065). Due to limited information, the clinical significance of the p.Ser762Asn variant is uncertain at this time. While the population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of the p.Ser762Asn variant is uncertain at this time. References: Mazzoni SM and Fearon ER. AXIN1 and AXIN2 variants in gastrointestinal cancers. Cancer Lett. 2014 Dec 1;355(1):1-8.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002228347	SCV002511698	likely benign	not specified	2022-04-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001015062	SCV002537168	benign	Hereditary cancer-predisposing syndrome	2020-11-06	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002228347	SCV002551229	uncertain significance	not specified	2024-07-31	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000656577	SCV000778626	uncertain significance	not provided	2017-11-10	no assertion criteria provided	clinical testing
Center of Medical Genetics and Primary Health Care	RCV001269355	SCV001448704	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000656577	SCV001969719	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542823	SCV004761919	likely benign	AXIN2-related disorder	2019-11-22	no assertion criteria provided	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).