10-98461509-T-C

Position:

• chr10-98461509-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021828.5(HPSE2):​c.1614-1770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,130 control chromosomes in the GnomAD database, including 5,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5358 hom., cov: 33)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.10

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-98461509-T-C is Benign according to our data. Variant chr10-98461509-T-C is described in ClinVar as [Benign]. Clinvar id is 1223507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.1614-1770A>G		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.1614-1770A>G		intron_variant		1	NM_021828.5	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38424 AN: 152012 Hom.: 5360 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.253 AC: 38427 AN: 152130 Hom.: 5358 Cov.: 33 AF XY: 0.249 AC XY: 18542 AN XY: 74366

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.275

Alfa AF: 0.295 Hom.: 2707

Bravo AF: 0.248

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0030
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs10883104; hg19: chr10-100221266;