chr4-79983878-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_058172.6(ANTXR2):​c.1179G>A​(p.Glu393Glu) variant causes a splice region, synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ANTXR2
NM_058172.6 splice_region, synonymous

Scores

2
Splicing: ADA: 1.000
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.57
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 4: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, phyloP100way_vertebrate [when BayesDel_noAF, Dann was below the threshold]
PP5
Variant 4-79983878-C-T is Pathogenic according to our data. Variant chr4-79983878-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2598.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANTXR2NM_058172.6 linkc.1179G>A p.Glu393Glu splice_region_variant, synonymous_variant 14/17 ENST00000403729.7 NP_477520.2 P58335-4
ANTXR2NM_001145794.2 linkc.1179G>A p.Glu393Glu splice_region_variant, synonymous_variant 14/16 NP_001139266.1 P58335-1
ANTXR2NM_001286780.2 linkc.948G>A p.Glu316Glu splice_region_variant, synonymous_variant 14/17 NP_001273709.1 P58335J3KPY9Q32Q26
ANTXR2NM_001286781.2 linkc.948G>A p.Glu316Glu splice_region_variant, synonymous_variant 14/17 NP_001273710.1 P58335J3KPY9A4FUA5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANTXR2ENST00000403729.7 linkc.1179G>A p.Glu393Glu splice_region_variant, synonymous_variant 14/171 NM_058172.6 ENSP00000385575.2 P58335-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457044
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
724954
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hyaline fibromatosis syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 01, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
1.0
SpliceAI score (max)
0.60
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.36
Position offset: -39
DS_DL_spliceai
0.60
Position offset: 0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs546102223; hg19: chr4-80905032; API