NM_021828.5:c.1736A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021828.5(HPSE2):c.1736A>T(p.Tyr579Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,613,592 control chromosomes in the GnomAD database, including 201,094 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21512 hom., cov: 32)

Exomes 𝑓: 0.49 ( 179582 hom. )

Consequence

HPSE2
NM_021828.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 7.54

Publications

32 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

HPSE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.144491E-4).

BP6

Variant 10-98459617-T-A is Benign according to our data. Variant chr10-98459617-T-A is described in ClinVar as [Benign]. Clinvar id is 802626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5 link	c.1736A>T	p.Tyr579Phe	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
HPSE2	ENST00000370552.8 link	c.1736A>T	p.Tyr579Phe	missense_variant	Exon 12 of 12	1	NM_021828.5	ENSP00000359583.3		Q8WWQ2-1

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

80142

AN:

151876

Hom.:

21498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.551

GnomAD2 exomes

AF:

0.505

AC:

126889

AN:

251258

AF XY:

0.499

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.462

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.520

GnomAD4 exome

AF:

0.494

AC:

721963

AN:

1461598

Hom.:

179582

Cov.:

AF XY:

0.492

AC XY:

357691

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.628

AC:

21008

AN:

33476

American (AMR)

AF:

0.514

AC:

22990

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

17235

AN:

26134

East Asian (EAS)

AF:

0.565

AC:

22431

AN:

39696

South Asian (SAS)

AF:

0.439

AC:

37900

AN:

86254

European-Finnish (FIN)

AF:

0.475

AC:

25361

AN:

53408

Middle Eastern (MID)

AF:

0.531

AC:

3062

AN:

5766

European-Non Finnish (NFE)

AF:

0.487

AC:

541263

AN:

1111756

Other (OTH)

AF:

0.509

AC:

30713

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

21706

43413

65119

86826

108532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.528

AC:

80211

AN:

151994

Hom.:

21512

Cov.:

AF XY:

0.525

AC XY:

38984

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.617

AC:

25559

AN:

41446

American (AMR)

AF:

0.511

AC:

7809

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.660

AC:

2290

AN:

3470

East Asian (EAS)

AF:

0.531

AC:

2732

AN:

5142

South Asian (SAS)

AF:

0.454

AC:

2183

AN:

4810

European-Finnish (FIN)

AF:

0.449

AC:

4755

AN:

10580

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33139

AN:

67958

Other (OTH)

AF:

0.547

AC:

1154

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1940

3880

5819

7759

9699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.509

Hom.:

15044

Bravo

AF:

0.542

TwinsUK

AF:

0.484

AC:

1795

ALSPAC

AF:

0.498

AC:

1920

ESP6500AA

AF:

0.621

AC:

2738

ESP6500EA

AF:

0.487

AC:

4185

ExAC

AF:

0.504

AC:

61157

Asia WGS

AF:

0.526

AC:

1831

AN:

3478

EpiCase

AF:

0.492

EpiControl

AF:

0.490

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Urofacial syndrome type 1

Benign:2

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.19

.;T;.;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

T;T;T;T

MetaRNN

Benign

0.00011

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.65

.;N;.;.

PhyloP100

7.5

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.63

.;N;N;.

REVEL

Benign

0.15

Sift

Benign

1.0

.;T;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010, 1.0

.;B;D;D

Vest4

0.24, 0.32, 0.51

MPC

0.15

ClinPred

0.037

GERP RS

5.3

Varity_R

0.19

gMVP

0.59

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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NM_021828.5:c.1736A>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over