4-79984831-AG-AGGG

Variant names:

• chr4-79984831-A-AGG
• rs312262690
• NM_058172.6:c.1072_1073dupCC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_058172.6(ANTXR2):​c.1072_1073dupCC​(p.Ala359LeufsTer51) variant causes a frameshift 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANTXR2 NM_058172.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 15 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: Pathogenic. The variant received 10 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

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.1072_1073dupCC	p.Ala359LeufsTer51	frameshift	Exon 13 of 17	NP_477520.2	P58335-4
	ANTXR2	NM_001145794.2		c.1072_1073dupCC	p.Ala359LeufsTer51	frameshift	Exon 13 of 16	NP_001139266.1	P58335-1
	ANTXR2	NM_001286780.2		c.841_842dupCC	p.Ala282LeufsTer51	frameshift	Exon 13 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.1072_1073dupCC	p.Ala359LeufsTer51	frameshift	Exon 13 of 17	ENSP00000385575.2	P58335-4
	ANTXR2	ENST00000307333.7	TSL:1	c.1072_1073dupCC	p.Ala359LeufsTer51	frameshift	Exon 13 of 16	ENSP00000306185.6	P58335-1
	ANTXR2	ENST00000404191.5	TSL:1	c.841_842dupCC	p.Ala282LeufsTer51	frameshift	Exon 13 of 17	ENSP00000384028.1	J3KPY9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454594 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723282

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.00 AC: 0 AN: 85076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107452

Other (OTH) AF: 0.00 AC: 0 AN: 60156

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs312262690; hg19: chr4-80905985;