10-98599129-C-T

Variant names:

• chr10-98599129-C-T
• rs11189705
• NM_021828.5:c.1320+15775G>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.1320+15775G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,968 control chromosomes in the GnomAD database, including 16,236 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 0.43 (16236 hom., cov: 31)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 1 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 (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1320+15775G>A		intron_variant	Intron 9 of 11	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.1320+15775G>A		intron_variant	Intron 9 of 11	1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64721 AN: 151848 Hom.: 16231 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.426 AC: 64739 AN: 151968 Hom.: 16236 Cov.: 31 AF XY: 0.431 AC XY: 32020 AN XY: 74268

African (AFR) AF: 0.144 AC: 5950 AN: 41456

American (AMR) AF: 0.537 AC: 8199 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2156 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2284 AN: 5144

South Asian (SAS) AF: 0.500 AC: 2408 AN: 4816

European-Finnish (FIN) AF: 0.574 AC: 6062 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36079 AN: 67948

Other (OTH) AF: 0.470 AC: 988 AN: 2102

Alfa AF: 0.494 Hom.: 6828

Bravo AF: 0.413

Asia WGS AF: 0.413 AC: 1438 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	5.3
DANN	Benign	0.43
PhyloP100		0.44
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: rs11189705; hg19: chr10-100358886;