rs17470570

Variant names:

• chr10-98820366-A-G
• rs17470570
• NM_021828.5:c.611-76310T>C

Variant summary

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

The NM_021828.5(HPSE2):​c.611-76310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,274 control chromosomes in the GnomAD database, including 197 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 0.043 (197 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.611-76310T>C		intron_variant	Intron 3 of 11	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.611-76310T>C		intron_variant	Intron 3 of 11	1	NM_021828.5	ENSP00000359583.3
HPSE2	ENST00000370546.5	c.611-76310T>C		intron_variant	Intron 3 of 12	1		ENSP00000359577.1
HPSE2	ENST00000370549.5	c.611-98538T>C		intron_variant	Intron 3 of 10	1		ENSP00000359580.1
HPSE2	ENST00000628193.2	c.449-98538T>C		intron_variant	Intron 2 of 9	1		ENSP00000485916.1

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6486 AN: 152156 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0426 AC: 6486 AN: 152274 Hom.: 197 Cov.: 32 AF XY: 0.0405 AC XY: 3014 AN XY: 74466

African (AFR) AF: 0.0109 AC: 454 AN: 41578

American (AMR) AF: 0.0237 AC: 363 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 65 AN: 3464

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5192

South Asian (SAS) AF: 0.0444 AC: 214 AN: 4822

European-Finnish (FIN) AF: 0.0476 AC: 505 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0697 AC: 4741 AN: 67992

Other (OTH) AF: 0.0340 AC: 72 AN: 2116

Alfa AF: 0.0533 Hom.: 53

Bravo AF: 0.0376

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.38
PhyloP100		-1.2
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: rs17470570; hg19: chr10-100580123;