rs11189853

Variant names:

• chr10-98886424-A-G
• rs11189853
• NM_021828.5:c.611-142368T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-98886424-A-G
• chr10-98886424-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021828.5(HPSE2):​c.611-142368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0958 in 152,150 control chromosomes in the GnomAD database, including 834 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 0.096 (834 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.611-142368T>C		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.611-142368T>C		intron_variant	Intron 3 of 11	1	NM_021828.5	ENSP00000359583.3
HPSE2	ENST00000370546.5	c.611-142368T>C		intron_variant	Intron 3 of 12	1		ENSP00000359577.1
HPSE2	ENST00000370549.5	c.611-164596T>C		intron_variant	Intron 3 of 10	1		ENSP00000359580.1
HPSE2	ENST00000628193.2	c.449-164596T>C		intron_variant	Intron 2 of 9	1		ENSP00000485916.1

Frequencies

GnomAD3 genomes AF: 0.0958 AC: 14568 AN: 152032 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0766

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

GnomAD4 genome AF: 0.0958 AC: 14576 AN: 152150 Hom.: 834 Cov.: 32 AF XY: 0.0963 AC XY: 7163 AN XY: 74370

African (AFR) AF: 0.0497 AC: 2064 AN: 41568

American (AMR) AF: 0.0506 AC: 772 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3466

East Asian (EAS) AF: 0.170 AC: 878 AN: 5172

South Asian (SAS) AF: 0.203 AC: 980 AN: 4824

European-Finnish (FIN) AF: 0.123 AC: 1306 AN: 10590

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

European-Non Finnish (NFE) AF: 0.120 AC: 8188 AN: 67966

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0925 Hom.: 413

Bravo AF: 0.0844

Asia WGS AF: 0.190 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.79
PhyloP100		0.43
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: rs11189853; hg19: chr10-100646181;