rs11189867

Variant names:

• chr10-98922691-T-C
• rs11189867
• NM_021828.5:c.611-178635A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

HPSE2 Gene-Disease associations (from GenCC):

• urofacial syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Ochoa syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.611-178635A>G		intron_variant	Intron 3 of 11	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.611-178635A>G		intron_variant	Intron 3 of 11	1	NM_021828.5	ENSP00000359583.3
HPSE2	ENST00000370546.5	c.611-178635A>G		intron_variant	Intron 3 of 12	1		ENSP00000359577.1
HPSE2	ENST00000370549.5	c.611-200863A>G		intron_variant	Intron 3 of 10	1		ENSP00000359580.1
HPSE2	ENST00000628193.2	c.449-200863A>G		intron_variant	Intron 2 of 9	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

African (AFR) AF: 0.0497 AC: 2065 AN: 41528

American (AMR) AF: 0.0488 AC: 747 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3468

East Asian (EAS) AF: 0.148 AC: 767 AN: 5170

South Asian (SAS) AF: 0.211 AC: 1018 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8220 AN: 68012

Other (OTH) AF: 0.0770 AC: 163 AN: 2116

Alfa AF: 0.109 Hom.: 1797

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
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11189867; hg19: chr10-100682448;