rs762313835

Variant names:

• chr10-98459653-C-A
• rs762313835
• NM_021828.5:c.1700G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-98459653-C-A
• chr10-98459653-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021828.5(HPSE2):​c.1700G>T​(p.Arg567Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: HPSE2 NM_021828.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.44

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPSE2	NM_021828.5	c.1700G>T	p.Arg567Leu	missense_variant	Exon 12 of 12	ENST00000370552.8	NP_068600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPSE2	ENST00000370552.8	c.1700G>T	p.Arg567Leu	missense_variant	Exon 12 of 12	1	NM_021828.5	ENSP00000359583.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 37

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T;.;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.6	.;L;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.3	.;N;N;.
REVEL	Uncertain	0.54
Sift	Benign	0.12	.;T;T;.
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.99, 1.0	.;D;D;D
Vest4		0.79, 0.75, 0.84
MutPred		0.50		.;Loss of methylation at R567 (P = 0.0442);.;.;
MVP		0.75
MPC		0.76
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.80

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: rs762313835; hg19: chr10-100219410;