rs11867417

Positions:

• chr17-65541780-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004655.4(AXIN2):​c.957-223A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,140 control chromosomes in the GnomAD database, including 26,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (26351 hom., cov: 33)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.293

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]

ENSG00000266076 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-65541780-T-C is Benign according to our data. Variant chr17-65541780-T-C is described in ClinVar as [Benign]. Clinvar id is 1281490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AXIN2	NM_004655.4	c.957-223A>G		intron_variant		ENST00000307078.10	NP_004646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AXIN2	ENST00000307078.10	c.957-223A>G		intron_variant		1	NM_004655.4	ENSP00000302625.5
AXIN2	ENST00000375702.5	c.957-223A>G		intron_variant		1		ENSP00000364854.5
ENSG00000266076	ENST00000577662.1	n.*1133-223A>G		intron_variant		2		ENSP00000462418.1
AXIN2	ENST00000618960.4	c.957-223A>G		intron_variant		5		ENSP00000478916.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86076 AN: 152022 Hom.: 26358 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.566 AC: 86077 AN: 152140 Hom.: 26351 Cov.: 33 AF XY: 0.564 AC XY: 41945 AN XY: 74394

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.564

Alfa AF: 0.605 Hom.: 5341

Bravo AF: 0.551

Asia WGS AF: 0.445 AC: 1550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.81

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: rs11867417; hg19: chr17-63537898;