10-98482438-C-T

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.1613+198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,128 control chromosomes in the GnomAD database, including 4,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4358 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.912

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=-0.88).
• BP6: Variant 10-98482438-C-T is Benign according to our data. Variant chr10-98482438-C-T is described in ClinVar as [Benign]. Clinvar id is 1183050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.1613+198G>A		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.1613+198G>A		intron_variant		1	NM_021828.5	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33403 AN: 152010 Hom.: 4356 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.220 AC: 33440 AN: 152128 Hom.: 4358 Cov.: 32 AF XY: 0.218 AC XY: 16214 AN XY: 74394

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.0957

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.249

Alfa AF: 0.181 Hom.: 3341

Bravo AF: 0.237

Asia WGS AF: 0.212 AC: 738 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.6
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs11189629; hg19: chr10-100242195;