rs1889974

Positions:

• chr10-98508763-A-G
• chr10-98508763-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021828.5(HPSE2):​c.1321-18567T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,996 control chromosomes in the GnomAD database, including 20,767 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 0.48 (20767 hom., cov: 31)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1321-18567T>C		intron_variant		ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.1321-18567T>C		intron_variant		1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72584 AN: 151878 Hom.: 20759 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.478 AC: 72592 AN: 151996 Hom.: 20767 Cov.: 31 AF XY: 0.483 AC XY: 35910 AN XY: 74294

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.534

Alfa AF: 0.592 Hom.: 53047

Bravo AF: 0.460

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.85
DANN	Benign	0.63

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: rs1889974; hg19: chr10-100268520;