dbSNP rs312262692: ANTXR2:p.Cys39Phe (chr4-80072445-C-A) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1PM2PP3

The NM_058172.6(ANTXR2):c.116G>T(p.Cys39Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANTXR2
NM_058172.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.82

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hyaline fibromatosis syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
juvenile hyaline fibromatosis
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
infantile systemic hyalinosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ANTXR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM1

In a disulfide_bond (size 179) in uniprot entity ANTR2_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_058172.6

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6 link	c.116G>T	p.Cys39Phe	missense_variant	Exon 1 of 17	ENST00000403729.7	NP_477520.2	P58335-4
ANTXR2	NM_001145794.2 link	c.116G>T	p.Cys39Phe	missense_variant	Exon 1 of 16		NP_001139266.1	P58335-1
ANTXR2	NM_001286780.2 link	c.-79-791G>T		intron_variant	Intron 1 of 16		NP_001273709.1	P58335J3KPY9Q32Q26
ANTXR2	NM_001286781.2 link	c.-80+264G>T		intron_variant	Intron 1 of 16		NP_001273710.1	P58335J3KPY9A4FUA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7 link	c.116G>T	p.Cys39Phe	missense_variant	Exon 1 of 17	1	NM_058172.6	ENSP00000385575.2		P58335-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455474

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724016

African (AFR)

AF:

0.00

AC:

AN:

32580

American (AMR)

AF:

0.00

AC:

AN:

44220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25876

East Asian (EAS)

AF:

0.00

AC:

AN:

38880

South Asian (SAS)

AF:

0.00

AC:

AN:

85338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109418

Other (OTH)

AF:

0.00

AC:

AN:

60140

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

.;.;D

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.86

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.83

D;D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.0

L;L;L

PhyloP100

4.8

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-7.9

D;D;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.84

MutPred

0.54

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.84

MPC

0.70

ClinPred

1.0

GERP RS

5.2

PromoterAI

0.059

Neutral

(source)

Varity_R

0.96

gMVP

0.78

Mutation Taster

=7/93

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over