10-98482352-T-G

Position:

• chr10-98482352-T-G

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+284A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,184 control chromosomes in the GnomAD database, including 3,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3568 hom., cov: 32)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.757

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=-0.82).
• BP6: Variant 10-98482352-T-G is Benign according to our data. Variant chr10-98482352-T-G is described in ClinVar as [Benign]. Clinvar id is 1235932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.1613+284A>C		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.1613+284A>C		intron_variant		1	NM_021828.5	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30908 AN: 152066 Hom.: 3564 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.203 AC: 30933 AN: 152184 Hom.: 3568 Cov.: 32 AF XY: 0.199 AC XY: 14778 AN XY: 74432

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.0910

Gnomad4 FIN AF: 0.0900

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.205

Alfa AF: 0.191 Hom.: 791

Bravo AF: 0.220

Asia WGS AF: 0.106 AC: 368 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	-0.82
CADD	Benign	4.5
DANN	Benign	0.47

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: rs35344122; hg19: chr10-100242109;