rs2801405

chr10-98824158-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.611-80102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,138 control chromosomes in the GnomAD database, including 49,163 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 0.80 (49163 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.611-80102G>A		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.611-80102G>A		intron_variant		1	NM_021828.5	P1
HPSE2	ENST00000370546.5	c.611-80102G>A		intron_variant		1
HPSE2	ENST00000370549.5	c.611-102330G>A		intron_variant		1
HPSE2	ENST00000628193.2	c.449-102330G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121786 AN: 152020 Hom.: 49111 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.801 AC: 121895 AN: 152138 Hom.: 49163 Cov.: 32 AF XY: 0.794 AC XY: 59076 AN XY: 74362

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.821

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.804

Alfa AF: 0.817 Hom.: 79532

Bravo AF: 0.798

Asia WGS AF: 0.725 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.7
Dann	Benign	0.46

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: rs2801405; hg19: chr10-100583915;