rs12509658

Variant names:

• chr4-80058255-G-C
• rs12509658
• NM_058172.6:c.297-2242C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-80058255-G-C
• chr4-80058255-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058172.6(ANTXR2):​c.297-2242C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,784 control chromosomes in the GnomAD database, including 12,704 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 0.38 (12704 hom., cov: 32)
• Consequence: ANTXR2 NM_058172.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6	c.297-2242C>G		intron_variant	Intron 3 of 16	ENST00000403729.7	NP_477520.2
ANTXR2	NM_001145794.2	c.297-2242C>G		intron_variant	Intron 3 of 15		NP_001139266.1
ANTXR2	NM_001286780.2	c.66-2242C>G		intron_variant	Intron 3 of 16		NP_001273709.1
ANTXR2	NM_001286781.2	c.66-2242C>G		intron_variant	Intron 3 of 16		NP_001273710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7	c.297-2242C>G		intron_variant	Intron 3 of 16	1	NM_058172.6	ENSP00000385575.2

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57857 AN: 151666 Hom.: 12698 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.381 AC: 57871 AN: 151784 Hom.: 12704 Cov.: 32 AF XY: 0.381 AC XY: 28243 AN XY: 74138

African (AFR) AF: 0.165 AC: 6831 AN: 41416

American (AMR) AF: 0.451 AC: 6863 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3468

East Asian (EAS) AF: 0.236 AC: 1210 AN: 5130

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4808

European-Finnish (FIN) AF: 0.504 AC: 5301 AN: 10522

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33201 AN: 67916

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.423 Hom.: 1840

Bravo AF: 0.369

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.5
DANN	Benign	0.32
PhyloP100		1.9
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: rs12509658; hg19: chr4-80979409;