rs4128941

chr17-65535213-G-Achr17-65535213-G-Cchr17-65535213-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004655.4(AXIN2):c.2237+413C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,242 control chromosomes in the GnomAD database, including 701 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 0.079 (701 hom., cov: 33)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN2	NM_004655.4	c.2237+413C>T		intron_variant		ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.2237+413C>T		intron_variant		1	NM_004655.4	P1
AXIN2	ENST00000375702.5	c.2042+413C>T		intron_variant		1
AXIN2	ENST00000618960.4	c.2042+413C>T		intron_variant		5
AXIN2	ENST00000578251.1	n.459+413C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12025 AN: 152124 Hom.: 683 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0793 AC: 12078 AN: 152242 Hom.: 701 Cov.: 33 AF XY: 0.0843 AC XY: 6274 AN XY: 74416

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0583

Gnomad4 FIN AF: 0.0727

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0482 Hom.: 645

Bravo AF: 0.0834

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.6
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs4128941; hg19: chr17-63531331;