ClinVar Miner

Submissions for variant NM_004655.4(AXIN2):c.1985T>C (p.Leu662Pro)

gnomAD frequency: 0.00084  dbSNP: rs142476324
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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115871 SCV000149780 likely benign not specified 2018-01-19 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.
Invitae RCV000203710 SCV000262219 likely benign Oligodontia-cancer predisposition syndrome 2024-02-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000203710 SCV000405687 benign Oligodontia-cancer predisposition syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Center for Human Genetics Tuebingen RCV000857875 SCV001151403 benign not provided 2022-10-01 criteria provided, single submitter clinical testing AXIN2: BS1, BS2
Ambry Genetics RCV001013914 SCV001174556 likely benign Hereditary cancer-predisposing syndrome 2018-10-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000857875 SCV001715460 uncertain significance not provided 2019-12-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000115871 SCV001737728 benign not specified 2021-06-07 criteria provided, single submitter clinical testing Variant summary: AXIN2 c.1985T>C (p.Leu662Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 245612 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 7 fold of the estimated maximal expected allele frequency for a pathogenic variant in AXIN2 causing Colorectal Cancer phenotype (0.00014), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1985T>C in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation with a predominant consensus as likely benign (n=3)/benign (n=1). Based on the evidence outlined above, the variant was classified as benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000857875 SCV002009784 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000857875 SCV002046907 benign not provided 2021-04-16 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001013914 SCV002537130 benign Hereditary cancer-predisposing syndrome 2020-09-29 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000115871 SCV002551243 uncertain significance not specified 2024-02-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000857875 SCV004564655 likely benign not provided 2023-09-18 criteria provided, single submitter clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000857875 SCV001799804 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000857875 SCV001919267 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000115871 SCV001929856 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000857875 SCV001971010 likely benign not provided no assertion criteria provided clinical testing

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