10-98469775-C-T

Variant names:

• chr10-98469775-C-T
• rs1998756
• NM_021828.5:c.1614-10036G>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.1614-10036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,130 control chromosomes in the GnomAD database, including 14,872 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 0.42 (14872 hom., cov: 33)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1614-10036G>A		intron_variant	Intron 11 of 11	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.1614-10036G>A		intron_variant	Intron 11 of 11	1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63627 AN: 152012 Hom.: 14833 Cov.: 33

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.419 AC: 63721 AN: 152130 Hom.: 14872 Cov.: 33 AF XY: 0.415 AC XY: 30852 AN XY: 74370

African (AFR) AF: 0.649 AC: 26942 AN: 41508

American (AMR) AF: 0.348 AC: 5317 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2021 AN: 5160

South Asian (SAS) AF: 0.288 AC: 1390 AN: 4822

European-Finnish (FIN) AF: 0.292 AC: 3094 AN: 10584

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.329 AC: 22370 AN: 67984

Other (OTH) AF: 0.389 AC: 822 AN: 2112

Alfa AF: 0.357 Hom.: 32035

Bravo AF: 0.434

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.67
PhyloP100		0.20
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: rs1998756; hg19: chr10-100229532;