dbSNP rs137852901: ANTXR2:p.Tyr381Phe (chr4-79983915-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_058172.6(ANTXR2):c.1142A>T(p.Tyr381Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,610,746 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ANTXR2
NM_058172.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.67

Variant links:

Genes affected

ANTXR2 (HGNC:21732): (ANTXR cell adhesion molecule 2) This gene encodes a receptor for anthrax toxin. The protein binds to collagen IV and laminin, suggesting that it may be involved in extracellular matrix adhesion. Mutations in this gene cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ANTXR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6 link	c.1142A>T	p.Tyr381Phe	missense_variant	Exon 14 of 17	ENST00000403729.7	NP_477520.2	P58335-4
ANTXR2	NM_001145794.2 link	c.1142A>T	p.Tyr381Phe	missense_variant	Exon 14 of 16		NP_001139266.1	P58335-1
ANTXR2	NM_001286780.2 link	c.911A>T	p.Tyr304Phe	missense_variant	Exon 14 of 17		NP_001273709.1	P58335J3KPY9Q32Q26
ANTXR2	NM_001286781.2 link	c.911A>T	p.Tyr304Phe	missense_variant	Exon 14 of 17		NP_001273710.1	P58335J3KPY9A4FUA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7 link	c.1142A>T	p.Tyr381Phe	missense_variant	Exon 14 of 17	1	NM_058172.6	ENSP00000385575.2		P58335-4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000810

AC:

AN:

246850

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

133986

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458696

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725524

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

.;.;.;D

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D;D;D

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.7

M;.;.;M

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.018

D;D;D;D

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.50

MutPred

0.51

Gain of glycosylation at Y380 (P = 0.0016);.;.;Gain of glycosylation at Y380 (P = 0.0016);

MVP

0.74

MPC

0.57

ClinPred

0.95

GERP RS

5.8

Varity_R

0.52

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over