rs2801405

Variant names:

• chr10-98824158-C-T
• rs2801405
• NM_021828.5:c.611-80102G>A

Variant summary

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

The NM_021828.5(HPSE2):​c.611-80102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,138 control chromosomes in the GnomAD database, including 49,163 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 0.80 (49163 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.611-80102G>A		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.611-80102G>A		intron_variant	Intron 3 of 11	1	NM_021828.5	ENSP00000359583.3
HPSE2	ENST00000370546.5	c.611-80102G>A		intron_variant	Intron 3 of 12	1		ENSP00000359577.1
HPSE2	ENST00000370549.5	c.611-102330G>A		intron_variant	Intron 3 of 10	1		ENSP00000359580.1
HPSE2	ENST00000628193.2	c.449-102330G>A		intron_variant	Intron 2 of 9	1		ENSP00000485916.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121786 AN: 152020 Hom.: 49111 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.801 AC: 121895 AN: 152138 Hom.: 49163 Cov.: 32 AF XY: 0.794 AC XY: 59076 AN XY: 74362

African (AFR) AF: 0.825 AC: 34238 AN: 41518

American (AMR) AF: 0.713 AC: 10892 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2756 AN: 3472

East Asian (EAS) AF: 0.648 AC: 3350 AN: 5172

South Asian (SAS) AF: 0.821 AC: 3951 AN: 4814

European-Finnish (FIN) AF: 0.736 AC: 7780 AN: 10570

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.828 AC: 56263 AN: 67990

Other (OTH) AF: 0.804 AC: 1699 AN: 2114

Alfa AF: 0.816 Hom.: 117717

Bravo AF: 0.798

Asia WGS AF: 0.725 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.46
PhyloP100		0.10
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: rs2801405; hg19: chr10-100583915;