10-98459505-G-T

Position:

• chr10-98459505-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021828.5(HPSE2):​c.*69C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,511,974 control chromosomes in the GnomAD database, including 1,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (205 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1223 hom.)
• Consequence: HPSE2 NM_021828.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.66

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-98459505-G-T is Benign according to our data. Variant chr10-98459505-G-T is described in ClinVar as [Benign]. Clinvar id is 1237632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.*69C>A		3_prime_UTR_variant	12/12	ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.*69C>A		3_prime_UTR_variant	12/12	1	NM_021828.5	P1
HPSE2	ENST00000370549.5	c.*69C>A		3_prime_UTR_variant	11/11	1
HPSE2	ENST00000628193.2	c.*69C>A		3_prime_UTR_variant	10/10	1
HPSE2	ENST00000404542.5	c.*69C>A		3_prime_UTR_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6988 AN: 152032 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0479

GnomAD4 exome AF: 0.0386 AC: 52497 AN: 1359824 Hom.: 1223 Cov.: 21 AF XY: 0.0383 AC XY: 26141 AN XY: 681972

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.0266

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.0000510

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0175

Gnomad4 NFE exome AF: 0.0425

Gnomad4 OTH exome AF: 0.0381

GnomAD4 genome AF: 0.0460 AC: 6994 AN: 152150 Hom.: 205 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74386

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.0373

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0474

Alfa AF: 0.0441 Hom.: 34

Bravo AF: 0.0511

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.62

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: rs35712968; hg19: chr10-100219262;