rs137852902

Positions:

• chr4-80055996-C-A
• chr4-80055996-C-G
• chr4-80055996-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM5

The ENST00000403729.7(ANTXR2):​c.314G>T​(p.Gly105Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G105D) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANTXR2 ENST00000403729.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 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 ENST00000403729.7
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr4-80055996-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2600.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANTXR2	NM_058172.6	c.314G>T	p.Gly105Val	missense_variant	4/17	ENST00000403729.7	NP_477520.2
ANTXR2	NM_001145794.2	c.314G>T	p.Gly105Val	missense_variant	4/16		NP_001139266.1
ANTXR2	NM_001286780.2	c.83G>T	p.Gly28Val	missense_variant	4/17		NP_001273709.1
ANTXR2	NM_001286781.2	c.83G>T	p.Gly28Val	missense_variant	4/17		NP_001273710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7	c.314G>T	p.Gly105Val	missense_variant	4/17	1	NM_058172.6	ENSP00000385575	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1410702 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 698208

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	.;.;.;D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	2.9	M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-8.3	D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.69
MutPred		0.53		Loss of disorder (P = 0.0311);.;Loss of disorder (P = 0.0311);Loss of disorder (P = 0.0311);
MVP		0.88
MPC		0.67
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.97
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs137852902; hg19: chr4-80977150;