chr17-65549504-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004655.4(AXIN2):c.956+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,611,332 control chromosomes in the GnomAD database, including 4,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.086 ( 847 hom., cov: 32)
Exomes 𝑓: 0.056 ( 3953 hom. )
Consequence
AXIN2
NM_004655.4 intron
NM_004655.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.674
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 17-65549504-T-C is Benign according to our data. Variant chr17-65549504-T-C is described in ClinVar as [Benign]. Clinvar id is 259516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-65549504-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.956+16A>G | intron_variant | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.956+16A>G | intron_variant | 1 | NM_004655.4 | P1 | |||
AXIN2 | ENST00000375702.5 | c.956+16A>G | intron_variant | 1 | |||||
AXIN2 | ENST00000618960.4 | c.956+16A>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0862 AC: 13104AN: 151982Hom.: 828 Cov.: 32
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GnomAD3 exomes AF: 0.0833 AC: 20597AN: 247344Hom.: 1423 AF XY: 0.0774 AC XY: 10354AN XY: 133700
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GnomAD4 exome AF: 0.0557 AC: 81226AN: 1459232Hom.: 3953 Cov.: 32 AF XY: 0.0550 AC XY: 39948AN XY: 725728
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GnomAD4 genome AF: 0.0865 AC: 13156AN: 152100Hom.: 847 Cov.: 32 AF XY: 0.0916 AC XY: 6809AN XY: 74354
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Oligodontia-cancer predisposition syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 28, 2016 | Variant Summary: The c.956+16A>G variant affects a non-conserved intronic nucleotide at an intronic position not widely known to affect splicing. MutationTaster predicts benign outcome for this variant. In addition, 5/5 splice-site tools in Alamut predict that this variant does not affect normal splicing. This variant is found in 9192/108058 control chromosomes from the large and broad populations of ExAC (including 609 homozygotes) at a frequency of 0.0850654, which is about 599 times greater than the maximal expected frequency of a pathogenic allele (0.0001421) in this gene, suggesting this variant is benign. Taken together, this variant has been classified as Benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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