dbSNP rs2862507: HPSE2:c.610+96205A>T (chr10-99048033-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021828.5(HPSE2):c.610+96205A>T variant causes a intron change. The variant allele was found at a frequency of 0.102 in 684,872 control chromosomes in the GnomAD database, including 4,258 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 823 hom., cov: 32)

Exomes 𝑓: 0.10 ( 3435 hom. )

Consequence

HPSE2
NM_021828.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.68

Publications

0 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 links:

RPL7P36 (HGNC:37045): (ribosomal protein L7 pseudogene 36)

RPL7P36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5 link	c.610+96205A>T		intron_variant	Intron 3 of 11	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.610+96205A>T		intron_variant	Intron 3 of 11	1	NM_021828.5	ENSP00000359583.3		Q8WWQ2-1

Frequencies

GnomAD3 genomes

AF:

0.0996

AC:

15156

AN:

152118

Hom.:

822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0461

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0980

Gnomad OTH

AF:

0.0712

GnomAD4 exome

AF:

0.103

AC:

55024

AN:

532636

Hom.:

3435

Cov.:

AF XY:

0.108

AC XY:

31033

AN XY:

287868

show subpopulations

African (AFR)

AF:

0.107

AC:

1610

AN:

15044

American (AMR)

AF:

0.0317

AC:

1031

AN:

32502

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

850

AN:

18242

East Asian (EAS)

AF:

0.122

AC:

3974

AN:

32568

South Asian (SAS)

AF:

0.178

AC:

10583

AN:

59434

European-Finnish (FIN)

AF:

0.119

AC:

3894

AN:

32690

Middle Eastern (MID)

AF:

0.0571

AC:

127

AN:

2224

European-Non Finnish (NFE)

AF:

0.0969

AC:

30112

AN:

310636

Other (OTH)

AF:

0.0970

AC:

2843

AN:

29296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2535

5069

7604

10138

12673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0997

AC:

15175

AN:

152236

Hom.:

823

Cov.:

AF XY:

0.0996

AC XY:

7414

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.110

AC:

4553

AN:

41550

American (AMR)

AF:

0.0461

AC:

704

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

162

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

739

AN:

5170

South Asian (SAS)

AF:

0.183

AC:

886

AN:

4832

European-Finnish (FIN)

AF:

0.118

AC:

1249

AN:

10612

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0980

AC:

6662

AN:

67998

Other (OTH)

AF:

0.0705

AC:

149

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

726

1453

2179

2906

3632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0524

Hom.:

Bravo

AF:

0.0918

Asia WGS

AF:

0.186

AC:

647

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

4.0

(source)

DANN

Benign

0.63

PhyloP100

5.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over