rs475945

Variant names:

• chr10-98659956-G-A
• rs475945
• NM_021828.5:c.1005-18016C>T

Variant summary

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

The NM_021828.5(HPSE2):​c.1005-18016C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,144 control chromosomes in the GnomAD database, including 1,984 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 0.14 (1984 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 3 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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 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.1005-18016C>T		intron	N/A	NP_068600.4
	HPSE2	NM_001166246.1		c.1005-18016C>T		intron	N/A	NP_001159718.1	Q8WWQ2-2
	HPSE2	NM_001166244.1		c.831-18016C>T		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.1005-18016C>T		intron	N/A	ENSP00000359583.3	Q8WWQ2-1
	HPSE2	ENST00000370546.5	TSL:1	c.1005-18016C>T		intron	N/A	ENSP00000359577.1	Q8WWQ2-2
	HPSE2	ENST00000370549.5	TSL:1	c.831-18016C>T		intron	N/A	ENSP00000359580.1	Q8WWQ2-3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21690 AN: 152026 Hom.: 1985 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.143 AC: 21682 AN: 152144 Hom.: 1984 Cov.: 32 AF XY: 0.147 AC XY: 10936 AN XY: 74368

African (AFR) AF: 0.0365 AC: 1518 AN: 41534

American (AMR) AF: 0.223 AC: 3411 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3462

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5174

South Asian (SAS) AF: 0.169 AC: 813 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2136 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11487 AN: 67982

Other (OTH) AF: 0.156 AC: 329 AN: 2108

Alfa AF: 0.159 Hom.: 372

Bravo AF: 0.140

Asia WGS AF: 0.197 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.6
DANN	Benign	0.35
PhyloP100		1.7
Mutation Taster		=98/2	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: rs475945; hg19: chr10-100419713;