rs748235355

Variant names:

• chr17-65537546-CAGGCGCCCGGCG-C
• rs748235355
• NM_004655.4:c.1478_1489delCGCCGGGCGCCT

Your query was ambiguous. Multiple possible variants found:

• chr17-65537546-CAGGCGCCCGGCG-C
• chr17-65537546-CAGGCGCCCGGCG-CAGGCGCCCGGCGAGGCGCCCGGCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_004655.4(AXIN2):​c.1478_1489delCGCCGGGCGCCT​(p.Ser493_Ala496del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S493S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AXIN2 NM_004655.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45
• Publications: 0 publications found

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, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• craniosynostosis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004655.4.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	NM_004655.4	MANE Select	c.1478_1489delCGCCGGGCGCCT	p.Ser493_Ala496del	disruptive_inframe_deletion	Exon 6 of 11	NP_004646.3
	AXIN2	NM_001363813.1		c.1478_1489delCGCCGGGCGCCT	p.Ser493_Ala496del	disruptive_inframe_deletion	Exon 6 of 10	NP_001350742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.1478_1489delCGCCGGGCGCCT	p.Ser493_Ala496del	disruptive_inframe_deletion	Exon 6 of 11	ENSP00000302625.5
	AXIN2	ENST00000375702.5	TSL:1	c.1478_1489delCGCCGGGCGCCT	p.Ser493_Ala496del	disruptive_inframe_deletion	Exon 5 of 9	ENSP00000364854.5
	AXIN2	ENST00000618960.4	TSL:5	c.1478_1489delCGCCGGGCGCCT	p.Ser493_Ala496del	disruptive_inframe_deletion	Exon 6 of 10	ENSP00000478916.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Oligodontia-cancer predisposition syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4
Mutation Taster		=159/41	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs748235355; hg19: chr17-63533664;