rs12570188

Positions:

• chr10-99095945-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.610+48293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 152,144 control chromosomes in the GnomAD database, including 93 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 0.016 (93 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.610+48293G>A		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.610+48293G>A		intron_variant		1	NM_021828.5	P1
HPSE2	ENST00000370546.5	c.610+48293G>A		intron_variant		1
HPSE2	ENST00000370549.5	c.610+48293G>A		intron_variant		1
HPSE2	ENST00000628193.2	c.448+136403G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2505 AN: 152026 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0636

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0164 AC: 2500 AN: 152144 Hom.: 93 Cov.: 32 AF XY: 0.0207 AC XY: 1543 AN XY: 74364

Gnomad4 AFR AF: 0.00354

Gnomad4 AMR AF: 0.0432

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0636

Gnomad4 NFE AF: 0.00250

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00862 Hom.: 1

Bravo AF: 0.0153

Asia WGS AF: 0.0620 AC: 214 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.77
DANN	Benign	0.41

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: rs12570188; hg19: chr10-100855702;