rs797045028

Variant names:

• chr4-79978048-TG-T
• rs797045028
• NM_058172.6:c.1305delC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_058172.6(ANTXR2):​c.1305delC​(p.Thr436HisfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANTXR2 NM_058172.6 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.766
• Publications: 1 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-79978048-TG-T is Pathogenic according to our data. Variant chr4-79978048-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 209132.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANTXR2	NM_058172.6	c.1305delC	p.Thr436HisfsTer24	frameshift_variant	Exon 15 of 17	ENST00000403729.7	NP_477520.2
ANTXR2	NM_001145794.2	c.1305delC	p.Thr436HisfsTer24	frameshift_variant	Exon 15 of 16		NP_001139266.1
ANTXR2	NM_001286780.2	c.1074delC	p.Thr359HisfsTer24	frameshift_variant	Exon 15 of 17		NP_001273709.1
ANTXR2	NM_001286781.2	c.1074delC	p.Thr359HisfsTer24	frameshift_variant	Exon 15 of 17		NP_001273710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANTXR2	ENST00000403729.7	c.1305delC	p.Thr436HisfsTer24	frameshift_variant	Exon 15 of 17	1	NM_058172.6	ENSP00000385575.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyaline fibromatosis syndrome Pathogenic:1

Jul 08, 2013

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This frameshift variant is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found once in our laboratory in trans with a missense variant [S81P] in a 21-year-old female with juvenile hyaline fibromatosis. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=5/195	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs797045028; hg19: chr4-80899202;