chr10-98459725-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_021828.5(HPSE2):​c.1628A>T​(p.Asn543Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,364 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 ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HPSE2
NM_021828.5 missense

Scores

11
7
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.54

Publications

5 publications found
Variant links:
Genes affected
HPSE2 (HGNC:18374): (heparanase 2 (inactive)) This gene encodes a heparanase enzyme. The encoded protein is a endoglycosidase that degrades heparin sulfate proteoglycans located on the extracellular matrix and cell surface. This protein may be involved in biological processes involving remodeling of the extracellular matrix including angiogenesis and tumor progression. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
HPSE2 Gene-Disease associations (from GenCC):
  • urofacial syndrome type 1
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • Ochoa syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.929
PP5
Variant 10-98459725-T-A is Pathogenic according to our data. Variant chr10-98459725-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 60719.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HPSE2NM_021828.5 linkc.1628A>T p.Asn543Ile missense_variant Exon 12 of 12 ENST00000370552.8 NP_068600.4 Q8WWQ2-1Q2M1H9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HPSE2ENST00000370552.8 linkc.1628A>T p.Asn543Ile missense_variant Exon 12 of 12 1 NM_021828.5 ENSP00000359583.3 Q8WWQ2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
249290
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461364
Hom.:
0
Cov.:
37
AF XY:
0.00000275
AC XY:
2
AN XY:
726934
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.00
AC:
0
AN:
44642
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86172
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53270
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111844
Other (OTH)
AF:
0.00
AC:
0
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Urofacial syndrome type 1 Pathogenic:1
Jan 01, 2012
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.75
.;D;.;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Pathogenic
0.54
D
MetaRNN
Pathogenic
0.93
D;D;D;D
MetaSVM
Uncertain
0.51
D
MutationAssessor
Uncertain
2.9
.;M;.;.
PhyloP100
7.5
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-7.3
.;D;D;.
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
.;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0, 1.0, 0.97
.;D;D;D
Vest4
0.99, 0.94, 0.92
MutPred
0.73
.;Loss of disorder (P = 0.0294);.;.;
MVP
0.85
MPC
0.76
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.91
gMVP
0.87
Mutation Taster
=2/98
disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs397515452; hg19: chr10-100219482; API