chr10-98634217-C-G

Variant names:

• chr10-98634217-C-G
• rs603269
• NM_021828.5:c.1098+7630G>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.1098+7630G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,150 control chromosomes in the GnomAD database, including 2,458 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 0.16 (2458 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• 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: 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE2	NM_021828.5	MANE Select	c.1098+7630G>C		intron	N/A	NP_068600.4
	HPSE2	NM_001166246.1		c.1098+7630G>C		intron	N/A	NP_001159718.1
	HPSE2	NM_001166244.1		c.924+7630G>C		intron	N/A	NP_001159716.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPSE2	ENST00000370552.8	TSL:1 MANE Select	c.1098+7630G>C		intron	N/A	ENSP00000359583.3
	HPSE2	ENST00000370546.5	TSL:1	c.1098+7630G>C		intron	N/A	ENSP00000359577.1
	HPSE2	ENST00000370549.5	TSL:1	c.924+7630G>C		intron	N/A	ENSP00000359580.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24217 AN: 152032 Hom.: 2460 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.173

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.159 AC: 24211 AN: 152150 Hom.: 2458 Cov.: 32 AF XY: 0.163 AC XY: 12116 AN XY: 74358

African (AFR) AF: 0.0412 AC: 1710 AN: 41548

American (AMR) AF: 0.234 AC: 3570 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3472

East Asian (EAS) AF: 0.138 AC: 713 AN: 5178

South Asian (SAS) AF: 0.177 AC: 853 AN: 4808

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10560

Middle Eastern (MID) AF: 0.179 AC: 52 AN: 290

European-Non Finnish (NFE) AF: 0.199 AC: 13520 AN: 67998

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.174 Hom.: 336

Bravo AF: 0.154

Asia WGS AF: 0.175 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
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: rs603269; hg19: chr10-100393974;