rs312262691

chr4-80018915-C-Achr4-80018915-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_058172.6(ANTXR2):c.928G>T(p.Val310Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000046 in 1,522,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ANTXR2 NM_058172.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.86
• PP5: Variant 4-80018915-C-A is Pathogenic according to our data. Variant chr4-80018915-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANTXR2	NM_058172.6	c.928G>T	p.Val310Phe	missense_variant	11/17	ENST00000403729.7
ANTXR2	NM_001145794.2	c.928G>T	p.Val310Phe	missense_variant	11/16
ANTXR2	NM_001286780.2	c.697G>T	p.Val233Phe	missense_variant	11/17
ANTXR2	NM_001286781.2	c.697G>T	p.Val233Phe	missense_variant	11/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANTXR2	ENST00000403729.7	c.928G>T	p.Val310Phe	missense_variant	11/17	1	NM_058172.6	P1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000292 AC: 4 AN: 1370218 Hom.: 0 Cov.: 29 AF XY: 0.00000148 AC XY: 1 AN XY: 674606

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: 0.00000374

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74320

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
Cadd	Benign	15
Dann	Uncertain	0.99
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	-0.0018	T
MutationAssessor	Uncertain	2.0	M;.;M
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.69	P;.;P
Vest4		0.83
MutPred		0.67		Loss of glycosylation at T311 (P = 0.0764);.;Loss of glycosylation at T311 (P = 0.0764);
MVP		0.76
MPC		0.46
ClinPred		0.98	D
GERP RS		-0.069
Varity_R		0.53
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs312262691; hg19: chr4-80940069;