Variant 10-98459762-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021828.5(HPSE2):c.1614-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,601,236 control chromosomes in the GnomAD database, including 198,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21471 hom., cov: 32)

Exomes 𝑓: 0.49 ( 177226 hom. )

Consequence

HPSE2
NM_021828.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.961

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 10-98459762-G-A is Benign according to our data. Variant chr10-98459762-G-A is described in ClinVar as [Benign]. Clinvar id is 1227966.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/exons	MANE	UniProt
HPSE2	NM_021828.5 linkuse as main transcript	c.1614-23C>T		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8 linkuse as main transcript	c.1614-23C>T		intron_variant		1	NM_021828.5	P1	Q8WWQ2-1

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

80030

AN:

151854

Hom.:

21457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.616

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.549

GnomAD3 exomes

AF:

0.501

AC:

115636

AN:

230840

Hom.:

28911

AF XY:

0.495

AC XY:

61849

AN XY:

124976

show subpopulations

Gnomad AFR exome

AF:

0.613

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.662

Gnomad EAS exome

AF:

0.537

Gnomad SAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.485

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.493

AC:

714200

AN:

1449264

Hom.:

177226

Cov.:

AF XY:

0.491

AC XY:

353287

AN XY:

720022

show subpopulations

Gnomad4 AFR exome

AF:

0.627

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.565

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.472

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.507

GnomAD4 genome

AF:

0.527

AC:

80098

AN:

151972

Hom.:

21471

Cov.:

AF XY:

0.524

AC XY:

38919

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.617

Gnomad4 AMR

AF:

0.512

Gnomad4 ASJ

AF:

0.660

Gnomad4 EAS

AF:

0.530

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.448

Gnomad4 NFE

AF:

0.487

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.506

Hom.:

26752

Bravo

AF:

0.541

Asia WGS

AF:

0.525

AC:

1828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Urofacial syndrome type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.77

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