2-69013669-T-TC

Variant names:

• chr2-69013669-T-TC
• rs200181645
• NM_032208.3:c.152+25dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_032208.3(ANTXR1):​c.152+25dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,551,014 control chromosomes in the GnomAD database, including 96 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (46 hom.)
• Consequence: ANTXR1 NM_032208.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120
• Publications: 0 publications found

Genes affected

ANTXR1 (HGNC:21014): (ANTXR cell adhesion molecule 1) This gene encodes a type I transmembrane protein and is a tumor-specific endothelial marker that has been implicated in colorectal cancer. The encoded protein has been shown to also be a docking protein or receptor for Bacillus anthracis toxin, the causative agent of the disease, anthrax. The binding of the protective antigen (PA) component, of the tripartite anthrax toxin, to this receptor protein mediates delivery of toxin components to the cytosol of cells. Once inside the cell, the other two components of anthrax toxin, edema factor (EF) and lethal factor (LF) disrupt normal cellular processes. Three alternatively spliced variants that encode different protein isoforms have been described. [provided by RefSeq, Oct 2008]

ANTXR1 Gene-Disease associations (from GenCC):

• GAPO syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• capillary infantile hemangioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300948 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-69013669-T-TC is Benign according to our data. Variant chr2-69013669-T-TC is described in ClinVar as Benign. ClinVar VariationId is 1971293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (2047/151996) while in subpopulation AFR AF = 0.0455 (1888/41462). AF 95% confidence interval is 0.0438. There are 50 homozygotes in GnomAd4. There are 979 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032208.3. 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
	ANTXR1	NM_032208.3	MANE Select	c.152+25dupC		intron	N/A	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.152+25dupC		intron	N/A	NP_444262.1	Q9H6X2-2
	ANTXR1	NM_001410840.1		c.152+25dupC		intron	N/A	NP_001397769.1	H0YC24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR1	ENST00000303714.9	TSL:1 MANE Select	c.152+18_152+19insC		intron	N/A	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000409349.7	TSL:1	c.152+18_152+19insC		intron	N/A	ENSP00000386494.3	Q9H6X2-2
	ANTXR1	ENST00000409829.7	TSL:1	c.152+18_152+19insC		intron	N/A	ENSP00000387058.3	Q9H6X2-4

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2038 AN: 151880 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00816

GnomAD2 exomes AF: 0.00365 AC: 557 AN: 152642 AF XY: 0.00323

Gnomad AFR exome AF: 0.0456

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.0000897

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000399

Gnomad OTH exome AF: 0.00323

GnomAD4 exome AF: 0.00162 AC: 2264 AN: 1399018 Hom.: 46 Cov.: 31 AF XY: 0.00152 AC XY: 1051 AN XY: 690028

African (AFR) AF: 0.0463 AC: 1462 AN: 31590

American (AMR) AF: 0.00269 AC: 96 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 298 AN: 25168

East Asian (EAS) AF: 0.0000839 AC: 3 AN: 35742

South Asian (SAS) AF: 0.000215 AC: 17 AN: 79222

European-Finnish (FIN) AF: 0.0000812 AC: 4 AN: 49244

Middle Eastern (MID) AF: 0.00469 AC: 26 AN: 5548

European-Non Finnish (NFE) AF: 0.000104 AC: 112 AN: 1078834

Other (OTH) AF: 0.00424 AC: 246 AN: 57964

GnomAD4 genome AF: 0.0135 AC: 2047 AN: 151996 Hom.: 50 Cov.: 32 AF XY: 0.0132 AC XY: 979 AN XY: 74296

African (AFR) AF: 0.0455 AC: 1888 AN: 41462

American (AMR) AF: 0.00543 AC: 83 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67932

Other (OTH) AF: 0.00807 AC: 17 AN: 2106

Alfa AF: 0.00373 Hom.: 2

Bravo AF: 0.0147

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism

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: rs200181645; hg19: chr2-69240801;