NM_021828.5:c.1321-46299G>A

Variant names:

• chr10-98536495-C-T
• rs536221
• NM_021828.5:c.1321-46299G>A

Variant summary

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

The NM_021828.5(HPSE2):​c.1321-46299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 151,852 control chromosomes in the GnomAD database, including 167 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 0.045 (167 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0816 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.1321-46299G>A		intron	N/A	NP_068600.4
	HPSE2	NM_001166246.1		c.1321-46299G>A		intron	N/A	NP_001159718.1
	HPSE2	NM_001166244.1		c.1147-46299G>A		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.1321-46299G>A		intron	N/A	ENSP00000359583.3
	HPSE2	ENST00000370546.5	TSL:1	c.1321-46299G>A		intron	N/A	ENSP00000359577.1
	HPSE2	ENST00000370549.5	TSL:1	c.1147-46299G>A		intron	N/A	ENSP00000359580.1

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6777 AN: 151736 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.0484

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0316

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

GnomAD4 genome AF: 0.0447 AC: 6786 AN: 151852 Hom.: 167 Cov.: 32 AF XY: 0.0444 AC XY: 3295 AN XY: 74196

African (AFR) AF: 0.0484 AC: 2005 AN: 41388

American (AMR) AF: 0.0285 AC: 434 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3468

East Asian (EAS) AF: 0.0416 AC: 214 AN: 5150

South Asian (SAS) AF: 0.0886 AC: 426 AN: 4810

European-Finnish (FIN) AF: 0.0221 AC: 233 AN: 10522

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0470 AC: 3193 AN: 67962

Other (OTH) AF: 0.0356 AC: 75 AN: 2108

Alfa AF: 0.0437 Hom.: 196

Bravo AF: 0.0426

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.39
PhyloP100		-0.77
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: rs536221; hg19: chr10-100296252;