17-65537614-ATGGTGGTGG-ATGGTGGTGGTGG
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_004655.4(AXIN2):c.1419_1421dupCCA(p.His474dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000545 in 1,580,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 0 hom. )
Consequence
AXIN2
NM_004655.4 disruptive_inframe_insertion
NM_004655.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.584
Genes affected
AXIN2 (HGNC:904): (axin 2) The Axin-related protein, Axin2, presumably plays an important role in the regulation of the stability of beta-catenin in the Wnt signaling pathway, like its rodent homologs, mouse conductin/rat axil. In mouse, conductin organizes a multiprotein complex of APC (adenomatous polyposis of the colon), beta-catenin, glycogen synthase kinase 3-beta, and conductin, which leads to the degradation of beta-catenin. Apparently, the deregulation of beta-catenin is an important event in the genesis of a number of malignancies. The AXIN2 gene has been mapped to 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Mutations in this gene have been associated with colorectal cancer with defective mismatch repair. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP6
Variant 17-65537614-A-ATGG is Benign according to our data. Variant chr17-65537614-A-ATGG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 234272.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=6, Uncertain_significance=5}.
BS2
High AC in GnomAd4 at 67 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1419_1421dupCCA | p.His474dup | disruptive_inframe_insertion | 6/11 | 1 | NM_004655.4 | ENSP00000302625.5 | ||
AXIN2 | ENST00000375702.5 | c.1419_1421dupCCA | p.His474dup | disruptive_inframe_insertion | 5/9 | 1 | ENSP00000364854.5 | |||
AXIN2 | ENST00000618960.4 | c.1419_1421dupCCA | p.His474dup | disruptive_inframe_insertion | 6/10 | 5 | ENSP00000478916.1 |
Frequencies
GnomAD3 genomes AF: 0.000442 AC: 67AN: 151668Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000302 AC: 63AN: 208906Hom.: 0 AF XY: 0.000275 AC XY: 31AN XY: 112800
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GnomAD4 exome AF: 0.000556 AC: 794AN: 1428892Hom.: 0 Cov.: 37 AF XY: 0.000535 AC XY: 380AN XY: 709644
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GnomAD4 genome AF: 0.000441 AC: 67AN: 151784Hom.: 0 Cov.: 32 AF XY: 0.000297 AC XY: 22AN XY: 74146
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:5Benign:8
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:3Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 04, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | AXIN2: BP3 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 04, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 30, 2023 | The AXIN2 c.1419_1421dup; p.His474dup variant (rs570443161), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 234272). This variant is observed in the general population with an overall allele frequency of 0.03% (74/240142 alleles) in the Genome Aggregation Database (v2.1.1). This variant inserts a single histidine residue leaving the rest of the protein in-frame. Due to limited information, the clinical significance of this variant is uncertain at this time. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2021 | This variant is associated with the following publications: (PMID: 28944238, 30404791, 27535533) - |
Oligodontia-cancer predisposition syndrome Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 05, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 11, 2022 | 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 01, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
AXIN2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 2024 | 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). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at