Variant 10-98482588-C-G 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.1613+48G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,611,768 control chromosomes in the GnomAD database, including 31,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 8891 hom., cov: 32)

Exomes 𝑓: 0.16 ( 22952 hom. )

Consequence

HPSE2
NM_021828.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.294

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 (BayesDel_noAF=-0.8).

BP6

Variant 10-98482588-C-G is Benign according to our data. Variant chr10-98482588-C-G is described in ClinVar as [Benign]. Clinvar id is 1226492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 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.1613+48G>C		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8 linkuse as main transcript	c.1613+48G>C		intron_variant		1	NM_021828.5	P1	Q8WWQ2-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42523

AN:

151880

Hom.:

8872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.581

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.201

AC:

50557

AN:

250936

Hom.:

6801

AF XY:

0.192

AC XY:

26064

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.591

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.159

AC:

231985

AN:

1459770

Hom.:

22952

Cov.:

AF XY:

0.158

AC XY:

114798

AN XY:

726336

show subpopulations

Gnomad4 AFR exome

AF:

0.598

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.193

GnomAD4 genome

AF:

0.280

AC:

42589

AN:

151998

Hom.:

8891

Cov.:

AF XY:

0.280

AC XY:

20790

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.581

Gnomad4 AMR

AF:

0.280

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.210

Hom.:

929

Bravo

AF:

0.303

Asia WGS

AF:

0.238

AC:

827

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.8

DANN

Benign

0.65

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