rs603269

chr10-98634217-C-Gchr10-98634217-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.1098+7630G>C		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.1098+7630G>C		intron_variant		1	NM_021828.5	P1

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

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.164

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs603269; hg19: chr10-100393974;