Genetic Variant ANTXR2:c.866+2948G>A (chr4-80028675-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_058172.6(ANTXR2):c.866+2948G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,014 control chromosomes in the GnomAD database, including 28,606 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 28606 hom., cov: 32)

Consequence

ANTXR2
NM_058172.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

41 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6 link	c.866+2948G>A	intron_variant	Intron 10 of 16	ENST00000403729.7	NP_477520.2	P58335-4
ANTXR2	NM_001145794.2 link	c.866+2948G>A	intron_variant	Intron 10 of 15		NP_001139266.1	P58335-1
ANTXR2	NM_001286780.2 link	c.635+2948G>A	intron_variant	Intron 10 of 16		NP_001273709.1	P58335J3KPY9Q32Q26
ANTXR2	NM_001286781.2 link	c.635+2948G>A	intron_variant	Intron 10 of 16		NP_001273710.1	P58335J3KPY9A4FUA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7 link	c.866+2948G>A		intron_variant	Intron 10 of 16	1	NM_058172.6	ENSP00000385575.2		P58335-4

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90490

AN:

151896

Hom.:

28586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.729

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.933

Gnomad SAS

AF:

0.772

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.596

AC:

90554

AN:

152014

Hom.:

28606

Cov.:

AF XY:

0.607

AC XY:

45055

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.388

AC:

16064

AN:

41454

American (AMR)

AF:

0.730

AC:

11141

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

2396

AN:

3472

East Asian (EAS)

AF:

0.934

AC:

4819

AN:

5162

South Asian (SAS)

AF:

0.772

AC:

3723

AN:

4822

European-Finnish (FIN)

AF:

0.676

AC:

7143

AN:

10572

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.637

AC:

43265

AN:

67952

Other (OTH)

AF:

0.605

AC:

1277

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1782

3564

5346

7128

8910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.636

Hom.:

78429

Bravo

AF:

0.589

Asia WGS

AF:

0.818

AC:

2842

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over