rs577969

Positions:

• chr10-98531419-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.1321-41223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 152,254 control chromosomes in the GnomAD database, including 159 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 0.044 (159 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1321-41223G>A		intron_variant		ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.1321-41223G>A		intron_variant		1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6722 AN: 152136 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0442 AC: 6731 AN: 152254 Hom.: 159 Cov.: 32 AF XY: 0.0438 AC XY: 3260 AN XY: 74442

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.0411

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0445 Hom.: 35

Bravo AF: 0.0422

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.69

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: rs577969; hg19: chr10-100291176;