Submissions for variant NM_004655.4(AXIN2):c.738C>A (p.Thr246=)

dbSNP: rs201191083

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000610628	SCV000723793	likely benign	not specified	2017-10-16	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001071632	SCV001236945	uncertain significance	Oligodontia-cancer predisposition syndrome	2019-03-26	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with AXIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 512736). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 246 of the AXIN2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the AXIN2 protein.
Ambry Genetics	RCV002385917	SCV002672404	likely benign	Hereditary cancer-predisposing syndrome	2019-08-21	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.
Myriad Genetics, Inc.	RCV001071632	SCV005083431	benign	Oligodontia-cancer predisposition syndrome	2024-06-27	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.