rs658053

Variant names:

• chr10-98624922-T-C
• rs658053
• NM_021828.5:c.1099-4214A>G

Variant summary

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

The NM_021828.5(HPSE2):​c.1099-4214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,142 control chromosomes in the GnomAD database, including 4,365 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 0.23 (4365 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1099-4214A>G		intron_variant	Intron 7 of 11	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.1099-4214A>G		intron_variant	Intron 7 of 11	1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35616 AN: 152024 Hom.: 4358 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.234 AC: 35660 AN: 152142 Hom.: 4365 Cov.: 32 AF XY: 0.237 AC XY: 17593 AN XY: 74362

African (AFR) AF: 0.201 AC: 8351 AN: 41524

American (AMR) AF: 0.315 AC: 4817 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 949 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1326 AN: 5166

South Asian (SAS) AF: 0.199 AC: 960 AN: 4820

European-Finnish (FIN) AF: 0.279 AC: 2954 AN: 10582

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.229 AC: 15539 AN: 67982

Other (OTH) AF: 0.240 AC: 507 AN: 2114

Alfa AF: 0.235 Hom.: 3384

Bravo AF: 0.241

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		-0.074
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: rs658053; hg19: chr10-100384679;