chr10-98540425-C-T

Variant names:

• chr10-98540425-C-T
• rs10786436
• NM_021828.5:c.1321-50229G>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.1321-50229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,966 control chromosomes in the GnomAD database, including 12,448 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 0.40 (12448 hom., cov: 33)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 16 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 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.1321-50229G>A		intron	N/A	NP_068600.4
	HPSE2	NM_001166246.1		c.1321-50229G>A		intron	N/A	NP_001159718.1	Q8WWQ2-2
	HPSE2	NM_001166244.1		c.1147-50229G>A		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.1321-50229G>A		intron	N/A	ENSP00000359583.3	Q8WWQ2-1
	HPSE2	ENST00000370546.5	TSL:1	c.1321-50229G>A		intron	N/A	ENSP00000359577.1	Q8WWQ2-2
	HPSE2	ENST00000370549.5	TSL:1	c.1147-50229G>A		intron	N/A	ENSP00000359580.1	Q8WWQ2-3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60127 AN: 151846 Hom.: 12436 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.396 AC: 60170 AN: 151966 Hom.: 12448 Cov.: 33 AF XY: 0.394 AC XY: 29240 AN XY: 74270

African (AFR) AF: 0.509 AC: 21067 AN: 41426

American (AMR) AF: 0.345 AC: 5271 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3468

East Asian (EAS) AF: 0.526 AC: 2717 AN: 5162

South Asian (SAS) AF: 0.349 AC: 1682 AN: 4822

European-Finnish (FIN) AF: 0.311 AC: 3283 AN: 10542

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23829 AN: 67948

Other (OTH) AF: 0.351 AC: 742 AN: 2112

Alfa AF: 0.345 Hom.: 13891

Bravo AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
DANN	Benign	0.54
PhyloP100		0.34
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: rs10786436; hg19: chr10-100300182;