Genetic Variant AXIN2:p.Pro600Ser (chr17-65536976-GGG-ACT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_004655.4(AXIN2):c.1798_1800delCCCinsAGT (p.Pro600Ser) variant causes a missense change. The gene AXIN2 is a tumor suppressor gene (CancerMine: 2 TSG, 1 oncogene citations). The gene AXIN2 is a known oncogene (CancerMine: 2 TSG, 1 oncogene citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.P600?: Uncertain_significance (ClinVar VariationId 1390478, 1 star); p.P600A: Uncertain_significance (ClinVar VariationId 1780298, 1 star); p.P600H: Uncertain_significance (ClinVar VariationId 1780307, 1 star); p.P600L: Uncertain_significance (ClinVar VariationId 2067600, 2 stars); p.P600= (synonymous): Benign/Likely_benign (ClinVar VariationId 464572, 2 stars); p.P600= (synonymous): Likely_benign (ClinVar VariationId 3224377, 1 star); p.P600S: Uncertain_significance (ClinVar VariationId 464571, 1 star)

Frequency

Genomes: not found (cov: 32)

Consequence

AXIN2
NM_004655.4 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.99

Publications

0 publications found

Variant links:

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]

AXIN2 Gene-Disease associations (from GenCC):

oligodontia-cancer predisposition syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
craniosynostosis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

AXIN2 links:

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new If you want to explore the variant's impact on the transcript NM_004655.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 points.

Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_004655.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	NM_004655.4	MANE Select	c.1798_1800delCCCinsAGT	p.Pro600Ser	missense	N/A	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.1712+346_1712+348delCCCinsAGT		intron	N/A	NP_001350742.1	E7ES00

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.1798_1800delCCCinsAGT	p.Pro600Ser	missense	N/A	ENSP00000302625.5	Q9Y2T1
AXIN2	ENST00000375702.5	TSL:1	c.1712+346_1712+348delCCCinsAGT		intron	N/A	ENSP00000364854.5	E7ES00
AXIN2	ENST00000881031.1		c.1798_1800delCCCinsAGT	p.Pro600Ser	missense	N/A	ENSP00000551090.1	Q9Y2T1

Frequencies

GnomAD3 genomes

Cov.:

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over