rs2487891

Variant names:

• chr10-99040075-T-C
• rs2487891
• NM_021828.5:c.610+104163A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021828.5(HPSE2):​c.610+104163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,620 control chromosomes in the GnomAD database, including 35,547 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 0.66 (35547 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021828.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE2	NM_021828.5	MANE Select	c.610+104163A>G		intron	N/A	NP_068600.4
	HPSE2	NM_001166246.1		c.610+104163A>G		intron	N/A	NP_001159718.1
	HPSE2	NM_001166244.1		c.610+104163A>G		intron	N/A	NP_001159716.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE2	ENST00000370552.8	TSL:1 MANE Select	c.610+104163A>G		intron	N/A	ENSP00000359583.3
	HPSE2	ENST00000370546.5	TSL:1	c.610+104163A>G		intron	N/A	ENSP00000359577.1
	HPSE2	ENST00000370549.5	TSL:1	c.610+104163A>G		intron	N/A	ENSP00000359580.1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99508 AN: 151502 Hom.: 35551 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.656 AC: 99533 AN: 151620 Hom.: 35547 Cov.: 32 AF XY: 0.662 AC XY: 49023 AN XY: 74062

African (AFR) AF: 0.347 AC: 14353 AN: 41390

American (AMR) AF: 0.738 AC: 11259 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2740 AN: 3462

East Asian (EAS) AF: 0.759 AC: 3901 AN: 5142

South Asian (SAS) AF: 0.735 AC: 3538 AN: 4812

European-Finnish (FIN) AF: 0.776 AC: 8132 AN: 10480

Middle Eastern (MID) AF: 0.684 AC: 197 AN: 288

European-Non Finnish (NFE) AF: 0.784 AC: 53133 AN: 67780

Other (OTH) AF: 0.689 AC: 1453 AN: 2110

Alfa AF: 0.734 Hom.: 103511

Bravo AF: 0.638

Asia WGS AF: 0.689 AC: 2394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2487891; hg19: chr10-100799832;