Variant 10-98459557-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021828.5(HPSE2):c.*17C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,611,968 control chromosomes in the GnomAD database, including 200,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21421 hom., cov: 32)

Exomes 𝑓: 0.49 ( 179245 hom. )

Consequence

HPSE2
NM_021828.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.310

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-98459557-G-A is Benign according to our data. Variant chr10-98459557-G-A is described in ClinVar as [Benign]. Clinvar id is 1228841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-98459557-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5 linkuse as main transcript	c.*17C>T		3_prime_UTR_variant	12/12	ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8 linkuse as main transcript	c.*17C>T		3_prime_UTR_variant	12/12	1	NM_021828.5	P1	Q8WWQ2-1

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

79943

AN:

151828

Hom.:

21407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.549

GnomAD3 exomes

AF:

0.504

AC:

126674

AN:

251114

Hom.:

32320

AF XY:

0.499

AC XY:

67754

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.512

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.539

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.520

GnomAD4 exome

AF:

0.494

AC:

720560

AN:

1460022

Hom.:

179245

Cov.:

AF XY:

0.491

AC XY:

357041

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.626

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.565

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.508

GnomAD4 genome

AF:

0.527

AC:

80012

AN:

151946

Hom.:

21421

Cov.:

AF XY:

0.524

AC XY:

38894

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.660

Gnomad4 EAS

AF:

0.530

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.487

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.510

Hom.:

20558

Bravo

AF:

0.541

Asia WGS

AF:

0.523

AC:

1822

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Urofacial syndrome type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.3

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over