chr10-98540425-C-T

Position:

• chr10-98540425-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.1321-50229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,966 control chromosomes in the GnomAD database, including 12,448 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 0.40 (12448 hom., cov: 33)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1321-50229G>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.1321-50229G>A		intron_variant		1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60127 AN: 151846 Hom.: 12436 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.396 AC: 60170 AN: 151966 Hom.: 12448 Cov.: 33 AF XY: 0.394 AC XY: 29240 AN XY: 74270

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.351

Alfa AF: 0.334 Hom.: 8760

Bravo AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
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: rs10786436; hg19: chr10-100300182;