17-65553370-A-C

Variant names:

• chr17-65553370-A-C
• rs3923086
• NM_004655.4:c.816-3710T>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.816-3710T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,008 control chromosomes in the GnomAD database, including 16,121 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 0.41 (16121 hom., cov: 31)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• Publications: 44 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.816-3710T>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.816-3710T>G		intron_variant	Intron 2 of 10	1	NM_004655.4	ENSP00000302625.5
AXIN2	ENST00000375702.5	c.816-3710T>G		intron_variant	Intron 1 of 8	1		ENSP00000364854.5
ENSG00000266076	ENST00000577662.1	n.*992-3710T>G		intron_variant	Intron 4 of 6	2		ENSP00000462418.1
AXIN2	ENST00000618960.4	c.816-3710T>G		intron_variant	Intron 2 of 9	5		ENSP00000478916.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62363 AN: 151890 Hom.: 16125 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.410 AC: 62343 AN: 152008 Hom.: 16121 Cov.: 31 AF XY: 0.409 AC XY: 30359 AN XY: 74284

African (AFR) AF: 0.106 AC: 4389 AN: 41518

American (AMR) AF: 0.463 AC: 7072 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3472

East Asian (EAS) AF: 0.163 AC: 843 AN: 5174

South Asian (SAS) AF: 0.412 AC: 1971 AN: 4782

European-Finnish (FIN) AF: 0.595 AC: 6271 AN: 10540

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38630 AN: 67930

Other (OTH) AF: 0.405 AC: 856 AN: 2114

Alfa AF: 0.513 Hom.: 44724

Bravo AF: 0.391

Asia WGS AF: 0.277 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.76
PhyloP100		0.57
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: rs3923086; hg19: chr17-63549488;