Submissions for variant NM_004655.4(AXIN2):c.2428G>A (p.Asp810Asn)

gnomAD frequency: 0.00123  dbSNP: rs140344858

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000115877	SCV000149786	uncertain significance	not provided	2018-09-06	criteria provided, single submitter	clinical testing	This variant is denoted AXIN2 c.2428G>A at the cDNA level, p.Asp810Asn (D810N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). This variant was observed in at least one individual with breast or gynecological cancer, as well as individuals with colon cancer (DeRycke 2017, Dominguez-Valentin 2018). AXIN2 Asp810Asn was observed at an allele frequency of 0.35% (83/24,028) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in the DIX domain (Salahshor 2005). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether AXIN2 Asp810Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080225	SCV000288702	benign	Oligodontia-cancer predisposition syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001015497	SCV001176337	likely benign	Hereditary cancer-predisposing syndrome	2019-04-15	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.
Sema4, Sema4	RCV001015497	SCV002537178	likely benign	Hereditary cancer-predisposing syndrome	2021-05-20	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002281937	SCV002571963	likely benign	not specified	2022-08-11	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002281937	SCV002773913	benign	not specified	2021-06-23	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002281937	SCV005089869	uncertain significance	not specified	2024-07-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542824	SCV004779090	likely benign	AXIN2-related disorder	2021-03-02	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).