2-69013519-G-A

Variant names:

• chr2-69013519-G-A
• rs28365986
• NM_032208.3:c.20G>A

Variant summary

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

The NM_032208.3(ANTXR1):​c.20G>A​(p.Arg7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,588,742 control chromosomes in the GnomAD database, including 650 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (51 hom., cov: 32)
  • Exomes 𝑓: 0.011 (599 hom.)
• Consequence: ANTXR1 NM_032208.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.648
• Publications: 9 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, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• capillary infantile hemangioma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300948 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014003515).
• BP6: Variant 2-69013519-G-A is Benign according to our data. Variant chr2-69013519-G-A is described in ClinVar as Benign. ClinVar VariationId is 1180103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

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.20G>A	p.Arg7Lys	missense	Exon 1 of 18	NP_115584.1	Q9H6X2-1
	ANTXR1	NM_053034.2		c.20G>A	p.Arg7Lys	missense	Exon 1 of 15	NP_444262.1	Q9H6X2-2
	ANTXR1	NM_001410840.1		c.20G>A	p.Arg7Lys	missense	Exon 1 of 13	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.20G>A	p.Arg7Lys	missense	Exon 1 of 18	ENSP00000301945.4	Q9H6X2-1
	ANTXR1	ENST00000409349.7	TSL:1	c.20G>A	p.Arg7Lys	missense	Exon 1 of 15	ENSP00000386494.3	Q9H6X2-2
	ANTXR1	ENST00000409829.7	TSL:1	c.20G>A	p.Arg7Lys	missense	Exon 1 of 13	ENSP00000387058.3	Q9H6X2-4

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1742 AN: 152222 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.0245 AC: 5024 AN: 205318 AF XY: 0.0242

Gnomad AFR exome AF: 0.000558

Gnomad AMR exome AF: 0.0256

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.117

Gnomad FIN exome AF: 0.0447

Gnomad NFE exome AF: 0.00295

Gnomad OTH exome AF: 0.0136

GnomAD4 exome AF: 0.0106 AC: 15160 AN: 1436402 Hom.: 599 Cov.: 31 AF XY: 0.0114 AC XY: 8115 AN XY: 711692

African (AFR) AF: 0.000360 AC: 12 AN: 33368

American (AMR) AF: 0.0245 AC: 967 AN: 39478

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 352 AN: 25528

East Asian (EAS) AF: 0.136 AC: 5263 AN: 38830

South Asian (SAS) AF: 0.0472 AC: 3860 AN: 81704

European-Finnish (FIN) AF: 0.0424 AC: 2182 AN: 51508

Middle Eastern (MID) AF: 0.00503 AC: 25 AN: 4966

European-Non Finnish (NFE) AF: 0.00161 AC: 1774 AN: 1101470

Other (OTH) AF: 0.0122 AC: 725 AN: 59550

GnomAD4 genome AF: 0.0114 AC: 1744 AN: 152340 Hom.: 51 Cov.: 32 AF XY: 0.0148 AC XY: 1103 AN XY: 74486

African (AFR) AF: 0.000505 AC: 21 AN: 41586

American (AMR) AF: 0.0132 AC: 202 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3468

East Asian (EAS) AF: 0.109 AC: 567 AN: 5180

South Asian (SAS) AF: 0.0501 AC: 242 AN: 4830

European-Finnish (FIN) AF: 0.0461 AC: 489 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68026

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00840 Hom.: 92

Bravo AF: 0.00860

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000457 AC: 2

ESP6500EA AF: 0.00222 AC: 19

ExAC AF: 0.0193 AC: 2289

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	ANTXR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.65
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.035
Sift	Benign	0.39	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.90
ClinPred		0.0029	T
GERP RS		-2.8
PromoterAI		0.041	Neutral
Varity_R		0.046
gMVP		0.40
Mutation Taster		=99/1	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: rs28365986; hg19: chr2-69240651; COSMIC: COSV58016613;