4-80018915-C-T

Variant names:

• chr4-80018915-C-T
• rs312262691
• NM_058172.6:c.928G>A
• ANTXR2 p.Val310Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_058172.6(ANTXR2):​c.928G>A​(p.Val310Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANTXR2 NM_058172.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 4 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: ClinGen, Labcorp Genetics (formerly Invitae)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09272084).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058172.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR2	NM_058172.6	MANE Select	c.928G>A	p.Val310Ile	missense	Exon 11 of 17	NP_477520.2	P58335-4
	ANTXR2	NM_001145794.2		c.928G>A	p.Val310Ile	missense	Exon 11 of 16	NP_001139266.1	P58335-1
	ANTXR2	NM_001286780.2		c.697G>A	p.Val233Ile	missense	Exon 11 of 17	NP_001273709.1	J3KPY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTXR2	ENST00000403729.7	TSL:1 MANE Select	c.928G>A	p.Val310Ile	missense	Exon 11 of 17	ENSP00000385575.2	P58335-4
	ANTXR2	ENST00000307333.7	TSL:1	c.928G>A	p.Val310Ile	missense	Exon 11 of 16	ENSP00000306185.6	P58335-1
	ANTXR2	ENST00000404191.5	TSL:1	c.697G>A	p.Val233Ile	missense	Exon 11 of 17	ENSP00000384028.1	J3KPY9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1370218 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 674606

African (AFR) AF: 0.00 AC: 0 AN: 29646

American (AMR) AF: 0.00 AC: 0 AN: 29276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24538

East Asian (EAS) AF: 0.00 AC: 0 AN: 34368

South Asian (SAS) AF: 0.00 AC: 0 AN: 71304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069166

Other (OTH) AF: 0.00 AC: 0 AN: 56980

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.83
DANN	Benign	0.27
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.015	N
PhyloP100		0.12
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.28
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.017
gMVP		0.073
Mutation Taster		=92/8	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs312262691;

hg19: chr4-80940069;