rs4541111

Positions:

• chr17-65538420-C-A

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.1060-77G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,587,454 control chromosomes in the GnomAD database, including 188,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (13643 hom., cov: 32)
  • Exomes 𝑓: 0.49 (174363 hom.)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.32

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-65538420-C-A is Benign according to our data. Variant chr17-65538420-C-A is described in ClinVar as [Benign]. Clinvar id is 1239471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN2	NM_004655.4	c.1060-77G>T		intron_variant		ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.1060-77G>T		intron_variant		1	NM_004655.4	P1
AXIN2	ENST00000375702.5	c.1060-77G>T		intron_variant		1
AXIN2	ENST00000618960.4	c.1060-77G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60903 AN: 151886 Hom.: 13645 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.488 AC: 700706 AN: 1435450 Hom.: 174363 AF XY: 0.486 AC XY: 346720 AN XY: 713388

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome AF: 0.401 AC: 60905 AN: 152004 Hom.: 13643 Cov.: 32 AF XY: 0.400 AC XY: 29695 AN XY: 74268

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.387

Alfa AF: 0.474 Hom.: 33757

Bravo AF: 0.389

Asia WGS AF: 0.337 AC: 1175 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

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.72

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: rs4541111; hg19: chr17-63534538; COSMIC: COSV61057494; COSMIC: COSV61057494;