10-98508763-A-G

Variant names:

• chr10-98508763-A-G
• rs1889974
• NM_021828.5:c.1321-18567T>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.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
• Publications: 10 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: G2P, Labcorp Genetics (formerly Invitae), 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 (SAS) allele frequency at 95% confidence interval = 0.626 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE2	NM_021828.5	MANE Select	c.1321-18567T>C		intron	N/A	NP_068600.4
	HPSE2	NM_001166246.1		c.1321-18567T>C		intron	N/A	NP_001159718.1	Q8WWQ2-2
	HPSE2	NM_001166244.1		c.1147-18567T>C		intron	N/A	NP_001159716.1	Q8WWQ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE2	ENST00000370552.8	TSL:1 MANE Select	c.1321-18567T>C		intron	N/A	ENSP00000359583.3	Q8WWQ2-1
	HPSE2	ENST00000370546.5	TSL:1	c.1321-18567T>C		intron	N/A	ENSP00000359577.1	Q8WWQ2-2
	HPSE2	ENST00000370549.5	TSL:1	c.1147-18567T>C		intron	N/A	ENSP00000359580.1	Q8WWQ2-3

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

African (AFR) AF: 0.140 AC: 5806 AN: 41488

American (AMR) AF: 0.572 AC: 8734 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2099 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2791 AN: 5150

South Asian (SAS) AF: 0.644 AC: 3105 AN: 4818

European-Finnish (FIN) AF: 0.630 AC: 6650 AN: 10556

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41614 AN: 67938

Other (OTH) AF: 0.534 AC: 1128 AN: 2114

Alfa AF: 0.573 Hom.: 109824

Bravo AF: 0.460

Asia WGS AF: 0.542 AC: 1886 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	0.85
DANN	Benign	0.63
PhyloP100		-1.3
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: rs1889974; hg19: chr10-100268520;