Submissions for variant NM_004655.4(AXIN2):c.2405+4A>G

gnomAD frequency: 0.00003  dbSNP: rs377423720

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000219901	SCV000279794	uncertain significance	not provided	2021-08-09	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000531592	SCV000639163	likely benign	Oligodontia-cancer predisposition syndrome	2025-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001015428	SCV001176257	benign	Hereditary cancer-predisposing syndrome	2024-09-10	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV001015428	SCV002537175	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-14	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465576	SCV002760993	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000219901	SCV005624984	uncertain significance	not provided	2024-01-15	criteria provided, single submitter	clinical testing	The AXIN2 c.2405+4A>G variant has not been reported in individuals with AXIN2-related conditions in the published literature. The frequency of this variant in the general population, 0.000093 (12/128926 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on AXIN2 mRNA splicing yielded inconclusive findings. Based on the available information, we are unable to determine the clinical significance of this variant.
PreventionGenetics, part of Exact Sciences	RCV004532818	SCV004735087	likely benign	AXIN2-related disorder	2024-01-02	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).