chr17-65528964-A-T

Variant names:

• chr17-65528964-A-T
• rs7591
• NM_004655.4:c.*1012T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000307078.10(AXIN2):​c.*1012T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 271,810 control chromosomes in the GnomAD database, including 40,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (20369 hom., cov: 33)
  • Exomes 𝑓: 0.56 (19652 hom.)
• Consequence: AXIN2 ENST00000307078.10 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00700
• Publications: 27 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-65528964-A-T is Benign according to our data. Variant chr17-65528964-A-T is described in ClinVar as Benign. ClinVar VariationId is 324630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000307078.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	NM_004655.4	MANE Select	c.*1012T>A		3_prime_UTR	Exon 11 of 11	NP_004646.3
	AXIN2	NM_001363813.1		c.*1012T>A		3_prime_UTR	Exon 10 of 10	NP_001350742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.*1012T>A		3_prime_UTR	Exon 11 of 11	ENSP00000302625.5
	AXIN2	ENST00000618960.4	TSL:5	c.*1012T>A		3_prime_UTR	Exon 10 of 10	ENSP00000478916.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75020 AN: 151986 Hom.: 20367 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.561 AC: 67134 AN: 119706 Hom.: 19652 Cov.: 0 AF XY: 0.564 AC XY: 32911 AN XY: 58306

African (AFR) AF: 0.250 AC: 1051 AN: 4208

American (AMR) AF: 0.551 AC: 2007 AN: 3642

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 3952 AN: 6016

East Asian (EAS) AF: 0.376 AC: 4504 AN: 11988

South Asian (SAS) AF: 0.557 AC: 3260 AN: 5852

European-Finnish (FIN) AF: 0.569 AC: 1198 AN: 2106

Middle Eastern (MID) AF: 0.522 AC: 396 AN: 758

European-Non Finnish (NFE) AF: 0.601 AC: 45737 AN: 76144

Other (OTH) AF: 0.559 AC: 5029 AN: 8992

GnomAD4 genome AF: 0.493 AC: 75023 AN: 152104 Hom.: 20369 Cov.: 33 AF XY: 0.493 AC XY: 36650 AN XY: 74344

African (AFR) AF: 0.253 AC: 10499 AN: 41500

American (AMR) AF: 0.536 AC: 8189 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2312 AN: 3472

East Asian (EAS) AF: 0.365 AC: 1887 AN: 5176

South Asian (SAS) AF: 0.566 AC: 2728 AN: 4822

European-Finnish (FIN) AF: 0.592 AC: 6252 AN: 10558

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41263 AN: 67972

Other (OTH) AF: 0.509 AC: 1074 AN: 2112

Alfa AF: 0.418 Hom.: 1255

Bravo AF: 0.481

Asia WGS AF: 0.422 AC: 1470 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Oligodontia-cancer predisposition syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.49
DANN	Benign	0.66
PhyloP100		-0.0070
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: rs7591; hg19: chr17-63525082;