rs10786455

Variant names:

• chr10-98694387-G-A
• rs10786455
• NM_021828.5:c.957-440C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-98694387-G-A
• chr10-98694387-G-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.957-440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,226 control chromosomes in the GnomAD database, including 252 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 0.039 (252 hom., cov: 33)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.957-440C>T		intron_variant	Intron 5 of 11	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.957-440C>T		intron_variant	Intron 5 of 11	1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5899 AN: 152108 Hom.: 250 Cov.: 33

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0389 AC: 5915 AN: 152226 Hom.: 252 Cov.: 33 AF XY: 0.0420 AC XY: 3127 AN XY: 74424

African (AFR) AF: 0.0768 AC: 3188 AN: 41526

American (AMR) AF: 0.0530 AC: 811 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3468

East Asian (EAS) AF: 0.170 AC: 879 AN: 5180

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4828

European-Finnish (FIN) AF: 0.0639 AC: 677 AN: 10590

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00294 AC: 200 AN: 68016

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0247 Hom.: 15

Bravo AF: 0.0405

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10786455; hg19: chr10-100454144;