rs11189867

Positions:

• chr10-98922691-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021828.5(HPSE2):​c.611-178635A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 152,220 control chromosomes in the GnomAD database, including 833 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 0.095 (833 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.611-178635A>G		intron_variant		ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.611-178635A>G		intron_variant		1	NM_021828.5	ENSP00000359583.3
HPSE2	ENST00000370546.5	c.611-178635A>G		intron_variant		1		ENSP00000359577.1
HPSE2	ENST00000370549.5	c.611-200863A>G		intron_variant		1		ENSP00000359580.1
HPSE2	ENST00000628193.2	c.449-200863A>G		intron_variant		1		ENSP00000485916.1

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14494 AN: 152102 Hom.: 834 Cov.: 32

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0769

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

GnomAD4 genome AF: 0.0953 AC: 14501 AN: 152220 Hom.: 833 Cov.: 32 AF XY: 0.0954 AC XY: 7100 AN XY: 74426

Gnomad4 AFR AF: 0.0497

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0770

Alfa AF: 0.103 Hom.: 465

Bravo AF: 0.0835

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.44

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: rs11189867; hg19: chr10-100682448;