17-65529488-CACTCCTAGCTCA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004655.4(AXIN2):c.*476_*487del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 289,820 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (4 hom.)
• Consequence: AXIN2 NM_004655.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.56

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 -10 ACMG points.

• BP6: Variant 17-65529488-CACTCCTAGCTCA-C is Benign according to our data. Variant chr17-65529488-CACTCCTAGCTCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 2648106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00439 (669/152316) while in subpopulation SAS AF= 0.00559 (27/4826). AF 95% confidence interval is 0.00467. There are 4 homozygotes in gnomad4. There are 340 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 669 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AXIN2	NM_004655.4	c.*476_*487del		3_prime_UTR_variant	11/11	ENST00000307078.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AXIN2	ENST00000307078.10	c.*476_*487del		3_prime_UTR_variant	11/11	1	NM_004655.4	P1
AXIN2	ENST00000618960.4	c.*476_*487del		3_prime_UTR_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 669 AN: 152198 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00511

Gnomad OTH AF: 0.00960

GnomAD4 exome AF: 0.00455 AC: 626 AN: 137504 Hom.: 4 AF XY: 0.00427 AC XY: 285 AN XY: 66734

Gnomad4 AFR exome AF: 0.00136

Gnomad4 AMR exome AF: 0.00523

Gnomad4 ASJ exome AF: 0.00443

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00515

Gnomad4 FIN exome AF: 0.00967

Gnomad4 NFE exome AF: 0.00503

Gnomad4 OTH exome AF: 0.00631

GnomAD4 genome AF: 0.00439 AC: 669 AN: 152316 Hom.: 4 Cov.: 32 AF XY: 0.00456 AC XY: 340 AN XY: 74482

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00512

Gnomad4 OTH AF: 0.00950

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00382

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

AXIN2: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs548756747; hg19: chr17-63525606;