10-98459762-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.961

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]

ACMG classification

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	c.1614-23C>T		intron_variant		ENST00000370552.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80030 AN: 151854 Hom.: 21457 Cov.: 32

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

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.: 33 AF XY: 0.491 AC XY: 353287 AN XY: 720022

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.: 32 AF XY: 0.524 AC XY: 38919 AN XY: 74284

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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	15
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

Other links and lift over

dbSNP: rs11189618; hg19: chr10-100219519; COSMIC: COSV65184041;