rs149533605
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004655.4(AXIN2):c.2439C>T(p.Ala813=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,614,124 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
AXIN2
NM_004655.4 synonymous
NM_004655.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.25
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 Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 17-65530069-G-A is Benign according to our data. Variant chr17-65530069-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 240015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.25 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00141 (215/152258) while in subpopulation AFR AF= 0.00503 (209/41524). AF 95% confidence interval is 0.00447. There are 1 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 215 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.2439C>T | p.Ala813= | synonymous_variant | 11/11 | ENST00000307078.10 | NP_004646.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.2439C>T | p.Ala813= | synonymous_variant | 11/11 | 1 | NM_004655.4 | ENSP00000302625 | P1 | |
AXIN2 | ENST00000375702.5 | c.2244C>T | p.Ala748= | synonymous_variant | 9/9 | 1 | ENSP00000364854 | |||
AXIN2 | ENST00000618960.4 | c.2244C>T | p.Ala748= | synonymous_variant | 10/10 | 5 | ENSP00000478916 |
Frequencies
GnomAD3 genomes AF: 0.00141 AC: 215AN: 152140Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000350 AC: 88AN: 251382Hom.: 1 AF XY: 0.000206 AC XY: 28AN XY: 135874
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GnomAD4 exome AF: 0.000129 AC: 188AN: 1461866Hom.: 1 Cov.: 31 AF XY: 0.0000976 AC XY: 71AN XY: 727232
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GnomAD4 genome AF: 0.00141 AC: 215AN: 152258Hom.: 1 Cov.: 33 AF XY: 0.00134 AC XY: 100AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 04, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 27, 2021 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 13, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 30, 2018 | 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. - |
Oligodontia-cancer predisposition syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at