rs7219582

Variant names:

• chr17-65537305-C-A
• rs7219582
• NM_004655.4:c.1712+19G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-65537305-C-A
• chr17-65537305-C-T

Variant summary

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

The NM_004655.4(AXIN2):​c.1712+19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,254 control chromosomes in the GnomAD database, including 11,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1939 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9750 hom.)
• Consequence: AXIN2 NM_004655.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.07
• Publications: 9 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: Ambry Genetics, ClinGen, 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=-0.93).
• BP6: Variant 17-65537305-C-A is Benign according to our data. Variant chr17-65537305-C-A is described in ClinVar as Benign. ClinVar VariationId is 259512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004655.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	NM_004655.4	MANE Select	c.1712+19G>T		intron	N/A	NP_004646.3	Q9Y2T1
	AXIN2	NM_001363813.1		c.1712+19G>T		intron	N/A	NP_001350742.1	E7ES00

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AXIN2	ENST00000307078.10	TSL:1 MANE Select	c.1712+19G>T		intron	N/A	ENSP00000302625.5	Q9Y2T1
	AXIN2	ENST00000375702.5	TSL:1	c.1712+19G>T		intron	N/A	ENSP00000364854.5	E7ES00
	AXIN2	ENST00000881031.1		c.1712+19G>T		intron	N/A	ENSP00000551090.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22342 AN: 152002 Hom.: 1934 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.119 AC: 29684 AN: 249130 AF XY: 0.120

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0796

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.0662

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.110 AC: 160860 AN: 1461134 Hom.: 9750 Cov.: 35 AF XY: 0.112 AC XY: 81634 AN XY: 726898

African (AFR) AF: 0.253 AC: 8472 AN: 33460

American (AMR) AF: 0.0845 AC: 3777 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3665 AN: 26136

East Asian (EAS) AF: 0.121 AC: 4814 AN: 39696

South Asian (SAS) AF: 0.164 AC: 14126 AN: 86218

European-Finnish (FIN) AF: 0.0647 AC: 3451 AN: 53364

Middle Eastern (MID) AF: 0.206 AC: 1104 AN: 5362

European-Non Finnish (NFE) AF: 0.102 AC: 113755 AN: 1111830

Other (OTH) AF: 0.128 AC: 7696 AN: 60344

GnomAD4 genome AF: 0.147 AC: 22370 AN: 152120 Hom.: 1939 Cov.: 32 AF XY: 0.145 AC XY: 10747 AN XY: 74352

African (AFR) AF: 0.246 AC: 10202 AN: 41486

American (AMR) AF: 0.116 AC: 1776 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.111 AC: 567 AN: 5120

South Asian (SAS) AF: 0.169 AC: 818 AN: 4826

European-Finnish (FIN) AF: 0.0574 AC: 608 AN: 10596

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7443 AN: 68008

Other (OTH) AF: 0.166 AC: 352 AN: 2116

Alfa AF: 0.126 Hom.: 2141

Bravo AF: 0.153

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	2	not specified (2)
-	-	2	Oligodontia-cancer predisposition syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.022
DANN	Benign	0.59
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs7219582; hg19: chr17-63533423;