rs2862507

Positions:

• chr10-99048033-T-A
• chr10-99048033-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021828.5(HPSE2):​c.610+96205A>T variant causes a intron change. The variant allele was found at a frequency of 0.102 in 684,872 control chromosomes in the GnomAD database, including 4,258 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (823 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3435 hom.)
• Consequence: HPSE2 NM_021828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68

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]

RPL7P36 (HGNC:37045): (ribosomal protein L7 pseudogene 36)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPSE2	NM_021828.5	c.610+96205A>T		intron_variant		ENST00000370552.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPSE2	ENST00000370552.8	c.610+96205A>T		intron_variant		1	NM_021828.5	P1
RPL7P36	ENST00000444633.1	n.395T>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0996 AC: 15156 AN: 152118 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.0712

GnomAD4 exome AF: 0.103 AC: 55024 AN: 532636 Hom.: 3435 Cov.: 5 AF XY: 0.108 AC XY: 31033 AN XY: 287868

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0317

Gnomad4 ASJ exome AF: 0.0466

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0969

Gnomad4 OTH exome AF: 0.0970

GnomAD4 genome AF: 0.0997 AC: 15175 AN: 152236 Hom.: 823 Cov.: 32 AF XY: 0.0996 AC XY: 7414 AN XY: 74452

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0980

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0524 Hom.: 53

Bravo AF: 0.0918

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.0
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2862507; hg19: chr10-100807790;