10-98459617-T-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr10-98459617-T-A is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.505

AC:

126889

AN:

251258

Hom.:

32407

AF XY:

0.499

AC XY:

67840

AN XY:

135858

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 SAS exome

AF:

0.444

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

Gnomad4 AFR exome

AF:

0.628

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.565

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.475

Gnomad4 NFE exome

AF:

0.487

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.528

AC:

80211

AN:

151994

Hom.:

21512

Cov.:

AF XY:

0.525

AC XY:

38984

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.660

Gnomad4 EAS

AF:

0.531

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.488

Gnomad4 OTH

AF:

0.547

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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;.;.

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

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over