Variant 4-80069491-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate

The NM_058172.6(ANTXR2):c.241T>C(p.Ser81Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,451,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ANTXR2
NM_058172.6 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.18

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1

In a disulfide_bond (size 179) in uniprot entity ANTR2_HUMAN there are 11 pathogenic changes around while only 2 benign (85%) in NM_058172.6

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.902

PP5

Variant 4-80069491-A-G is Pathogenic according to our data. Variant chr4-80069491-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 209133.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANTXR2	NM_058172.6 linkuse as main transcript	c.241T>C	p.Ser81Pro	missense_variant	3/17	ENST00000403729.7
ANTXR2	NM_001145794.2 linkuse as main transcript	c.241T>C	p.Ser81Pro	missense_variant	3/16
ANTXR2	NM_001286780.2 linkuse as main transcript	c.10T>C	p.Ser4Pro	missense_variant	3/17
ANTXR2	NM_001286781.2 linkuse as main transcript	c.10T>C	p.Ser4Pro	missense_variant	3/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR2	ENST00000403729.7 linkuse as main transcript	c.241T>C	p.Ser81Pro	missense_variant	3/17	1	NM_058172.6	P1	P58335-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451090

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hyaline fibromatosis syndrome

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Baylor Genetics

Jul 08, 2013

At time of reporting, this variant was novel. Likely pathogenicity based on finding it in trans with a deleterious frameshift variant [T436fs] in a 21-year-old female with juvenile hyaline fibromatosis. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

.;.;.;D

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.90

D;D;D;D

MetaSVM

Uncertain

0.23

MutationAssessor

Pathogenic

3.2

M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.3

D;D;D;D

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;D;D

Vest4

0.95

MutPred

0.71

Gain of glycosylation at S81 (P = 0.0395);.;Gain of glycosylation at S81 (P = 0.0395);Gain of glycosylation at S81 (P = 0.0395);

MVP

0.83

MPC

0.67

ClinPred

0.99

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.94

gMVP

0.94

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over