10-98531419-C-T

Variant names:

• chr10-98531419-C-T
• rs577969
• NM_021828.5:c.1321-41223G>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.1321-41223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 152,254 control chromosomes in the GnomAD database, including 159 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 0.044 (159 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1321-41223G>A		intron_variant	Intron 9 of 11	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.1321-41223G>A		intron_variant	Intron 9 of 11	1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6722 AN: 152136 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0442 AC: 6731 AN: 152254 Hom.: 159 Cov.: 32 AF XY: 0.0438 AC XY: 3260 AN XY: 74442

African (AFR) AF: 0.0481 AC: 1998 AN: 41530

American (AMR) AF: 0.0276 AC: 422 AN: 15310

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

East Asian (EAS) AF: 0.0411 AC: 212 AN: 5164

South Asian (SAS) AF: 0.0826 AC: 399 AN: 4832

European-Finnish (FIN) AF: 0.0219 AC: 232 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0469 AC: 3190 AN: 68022

Other (OTH) AF: 0.0350 AC: 74 AN: 2114

Alfa AF: 0.0467 Hom.: 292

Bravo AF: 0.0422

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.69
PhyloP100		-0.33
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: rs577969; hg19: chr10-100291176;