rs3923087

Variant names:

• chr17-65553143-T-C
• rs3923087
• NM_004655.4:c.816-3483A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004655.4(AXIN2):​c.816-3483A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,092 control chromosomes in the GnomAD database, including 30,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (30046 hom., cov: 32)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32
• Publications: 25 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

ENSG00000266076 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.816-3483A>G		intron_variant	Intron 2 of 10	ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.816-3483A>G		intron_variant	Intron 2 of 10	1	NM_004655.4	ENSP00000302625.5
AXIN2	ENST00000375702.5	c.816-3483A>G		intron_variant	Intron 1 of 8	1		ENSP00000364854.5
ENSG00000266076	ENST00000577662.1	n.*992-3483A>G		intron_variant	Intron 4 of 6	2		ENSP00000462418.1
AXIN2	ENST00000618960.4	c.816-3483A>G		intron_variant	Intron 2 of 9	5		ENSP00000478916.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88004 AN: 151972 Hom.: 30047 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.579 AC: 88001 AN: 152092 Hom.: 30046 Cov.: 32 AF XY: 0.578 AC XY: 43008 AN XY: 74368

African (AFR) AF: 0.213 AC: 8850 AN: 41490

American (AMR) AF: 0.590 AC: 9019 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2659 AN: 3466

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5168

South Asian (SAS) AF: 0.630 AC: 3033 AN: 4818

European-Finnish (FIN) AF: 0.791 AC: 8368 AN: 10580

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52048 AN: 67960

Other (OTH) AF: 0.573 AC: 1212 AN: 2114

Alfa AF: 0.708 Hom.: 87144

Bravo AF: 0.550

Asia WGS AF: 0.465 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.029
DANN	Benign	0.32
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3923087; hg19: chr17-63549261;