2-69013600-A-T

Position:

• chr2-69013600-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032208.3(ANTXR1):​c.101A>T​(p.Asp34Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANTXR1 NM_032208.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14029187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANTXR1	NM_032208.3	c.101A>T	p.Asp34Val	missense_variant	1/18	ENST00000303714.9	NP_115584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANTXR1	ENST00000303714.9	c.101A>T	p.Asp34Val	missense_variant	1/18	1	NM_032208.3	ENSP00000301945.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.101A>T (p.D34V) alteration is located in exon 1 (coding exon 1) of the ANTXR1 gene. This alteration results from a A to T substitution at nucleotide position 101, causing the aspartic acid (D) at amino acid position 34 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.80	T;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.069
Sift	Benign	0.073	T;T;D
Sift4G	Uncertain	0.0040	D;T;D
Polyphen		0.0010	B;B;B
Vest4		0.25
MutPred		0.37		Loss of disorder (P = 0.0177);Loss of disorder (P = 0.0177);Loss of disorder (P = 0.0177);
MVP		0.27
MPC		1.3
ClinPred		0.60	D
GERP RS		5.1
Varity_R		0.22
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-69240732;