Submissions for variant NM_004655.4(AXIN2):c.1952C>T (p.Ser651Leu)

gnomAD frequency: 0.00128  dbSNP: rs74006838

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000587836	SCV000149779	likely benign	not provided	2021-06-05	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28481359)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082227	SCV000288682	benign	Oligodontia-cancer predisposition syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587836	SCV000698518	benign	not provided	2017-06-23	criteria provided, single submitter	clinical testing	Variant summary: The AXIN2 c.1952C>T (p.Ser651Leu) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant. This variant was found in 47/117962 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.004176 (40/9578). This frequency is about 29 times the estimated maximal expected allele frequency of a pathogenic AXIN2 variant (0.0001421), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. An internal LCA sample reports the variant to co-occur with two MUTYH pathogenic variants, c.536A>G and c.1187G>A. Taken together, this variant is classified as benign.
Ambry Genetics	RCV001013820	SCV001174453	benign	Hereditary cancer-predisposing syndrome	2019-01-03	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587836	SCV001471475	likely benign	not provided	2022-03-31	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001013820	SCV002537124	benign	Hereditary cancer-predisposing syndrome	2020-09-10	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002505037	SCV002807054	likely benign	Oligodontia-cancer predisposition syndrome; Colorectal cancer	2022-05-27	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV003150945	SCV003839243	benign	not specified	2022-07-27	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542821	SCV004789702	benign	AXIN2-related disorder	2019-04-30	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).