Submissions for variant NM_004655.4(AXIN2):c.2083G>T (p.Ala695Ser)

gnomAD frequency: 0.00004  dbSNP: rs140510381

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000990052	SCV000559510	likely benign	Oligodontia-cancer predisposition syndrome	2025-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000484417	SCV000568391	uncertain significance	not provided	2022-02-22	criteria provided, single submitter	clinical testing	Observed in individuals with colon, breast, and/or ovarian cancer and in healthy controls (Khan 2011, Pritchard 2018, Moradian 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25236910, 21541676, 34426522, 29641532, 33558524)
Mendelics	RCV000990052	SCV001140816	benign	Oligodontia-cancer predisposition syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001014371	SCV001175069	likely benign	Hereditary cancer-predisposing syndrome	2022-12-30	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	RCV001014371	SCV002537148	likely benign	Hereditary cancer-predisposing syndrome	2021-12-08	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465674	SCV002760998	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Center of Medical Genetics and Primary Health Care	RCV001004836	SCV000987261	uncertain significance	Malignant tumor of breast	2020-04-08	no assertion criteria provided	research	This variant is in exon 6 in a non-functional domain. The allele frequency in GnomAD exomes is 0.000164 which is more than 0.0001 derived from the 1,065 clinically reported variants in gene AXIN2 (BS1 Benign Strong). This variant is also observed in healthy adults and GnomAD exomes allele count is 40 which is more than the threshold 5 for dominant gene AXIN2 (BS2 Benign Strong). Additionally, only 1 missense variant in AXIN2 gene is known to be pathogenic (BP1 Benign Supporting). In our study this variant was found in a 28-years-old female with unilateral breast cancer and no reported family history of cancer. Thus, we classified this variant as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV004541482	SCV004785812	likely benign	AXIN2-related disorder	2021-03-22	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).