4-80072228-G-C

Variant names:

• chr4-80072228-G-C
• rs6818557
• NM_058172.6:c.152+181C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058172.6(ANTXR2):​c.152+181C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,048 control chromosomes in the GnomAD database, including 44,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.76 (44609 hom., cov: 31)
• Consequence: ANTXR2 NM_058172.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.52
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-80072228-G-C is Benign according to our data. Variant chr4-80072228-G-C is described in ClinVar as Benign. ClinVar VariationId is 1279994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6	c.152+181C>G		intron_variant	Intron 1 of 16	ENST00000403729.7	NP_477520.2
ANTXR2	NM_001145794.2	c.152+181C>G		intron_variant	Intron 1 of 15		NP_001139266.1
ANTXR2	NM_001286780.2	c.-79-574C>G		intron_variant	Intron 1 of 16		NP_001273709.1
ANTXR2	NM_001286781.2	c.-80+481C>G		intron_variant	Intron 1 of 16		NP_001273710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7	c.152+181C>G		intron_variant	Intron 1 of 16	1	NM_058172.6	ENSP00000385575.2

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115168 AN: 151930 Hom.: 44582 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.901

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.758 AC: 115244 AN: 152048 Hom.: 44609 Cov.: 31 AF XY: 0.752 AC XY: 55894 AN XY: 74328

African (AFR) AF: 0.670 AC: 27769 AN: 41468

American (AMR) AF: 0.666 AC: 10179 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2108 AN: 5120

South Asian (SAS) AF: 0.826 AC: 3976 AN: 4816

European-Finnish (FIN) AF: 0.751 AC: 7954 AN: 10588

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.845 AC: 57431 AN: 67988

Other (OTH) AF: 0.774 AC: 1635 AN: 2112

Alfa AF: 0.780 Hom.: 2893

Bravo AF: 0.739

Asia WGS AF: 0.629 AC: 2190 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.70
DANN	Benign	0.38
PhyloP100		-2.5
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6818557; hg19: chr4-80993382;