dbSNP rs12570188: HPSE2:c.610+48293G>A (chr10-99095945-C-T) – 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+48293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 152,144 control chromosomes in the GnomAD database, including 93 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 0.016 ( 93 hom., cov: 32)

Consequence

HPSE2
NM_021828.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.469

Publications

13 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5 link	c.610+48293G>A		intron_variant	Intron 3 of 11	ENST00000370552.8	NP_068600.4	Q8WWQ2-1Q2M1H9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HPSE2	ENST00000370552.8 link	c.610+48293G>A	intron_variant	Intron 3 of 11	1	NM_021828.5	ENSP00000359583.3	Q8WWQ2-1
HPSE2	ENST00000370546.5 link	c.610+48293G>A	intron_variant	Intron 3 of 12	1		ENSP00000359577.1	Q8WWQ2-2
HPSE2	ENST00000370549.5 link	c.610+48293G>A	intron_variant	Intron 3 of 10	1		ENSP00000359580.1	Q8WWQ2-3
HPSE2	ENST00000628193.2 link	c.448+136403G>A	intron_variant	Intron 2 of 9	1		ENSP00000485916.1	Q8WWQ2-4

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2505

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0433

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.0636

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.0158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0164

AC:

2500

AN:

152144

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1543

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00354

AC:

147

AN:

41534

American (AMR)

AF:

0.0432

AC:

660

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.144

AC:

747

AN:

5170

South Asian (SAS)

AF:

0.0106

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0636

AC:

672

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00250

AC:

170

AN:

67992

Other (OTH)

AF:

0.0152

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

121

242

363

484

605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00869

Hom.:

Bravo

AF:

0.0153

Asia WGS

AF:

0.0620

AC:

214

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.77

(source)

DANN

Benign

0.41

PhyloP100

-0.47

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over