NM_058172.6:c.1142A>G

Variant names:

• chr4-79983915-T-C
• rs137852901
• NM_058172.6:c.1142A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_058172.6(ANTXR2):​c.1142A>G​(p.Tyr381Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANTXR2 NM_058172.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.67
• Publications: 10 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803
• PP5: Variant 4-79983915-T-C is Pathogenic according to our data. Variant chr4-79983915-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2599.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6	c.1142A>G	p.Tyr381Cys	missense_variant	Exon 14 of 17	ENST00000403729.7	NP_477520.2
ANTXR2	NM_001145794.2	c.1142A>G	p.Tyr381Cys	missense_variant	Exon 14 of 16		NP_001139266.1
ANTXR2	NM_001286780.2	c.911A>G	p.Tyr304Cys	missense_variant	Exon 14 of 17		NP_001273709.1
ANTXR2	NM_001286781.2	c.911A>G	p.Tyr304Cys	missense_variant	Exon 14 of 17		NP_001273710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7	c.1142A>G	p.Tyr381Cys	missense_variant	Exon 14 of 17	1	NM_058172.6	ENSP00000385575.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hyaline fibromatosis syndrome Pathogenic:1

Apr 01, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	.;.;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D;D;D;D
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.2	M;.;.;M
PhyloP100		7.7
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-7.5	D;D;D;D
REVEL	Uncertain	0.59
Sift	Benign	0.052	T;T;D;T
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.82
MutPred		0.63		Gain of glycosylation at Y380 (P = 0.0016);.;.;Gain of glycosylation at Y380 (P = 0.0016);
MVP		0.81
MPC		0.66
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.85
Mutation Taster		=6/94	disease causing (ClinVar)

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: rs137852901; hg19: chr4-80905069;