rs267606865
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_021828.5(HPSE2):c.457C>T(p.Arg153Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
HPSE2
NM_021828.5 stop_gained
NM_021828.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.41
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPSE2 | NM_021828.5 | c.457C>T | p.Arg153Ter | stop_gained | 3/12 | ENST00000370552.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPSE2 | ENST00000370552.8 | c.457C>T | p.Arg153Ter | stop_gained | 3/12 | 1 | NM_021828.5 | P1 | |
HPSE2 | ENST00000370546.5 | c.457C>T | p.Arg153Ter | stop_gained | 3/13 | 1 | |||
HPSE2 | ENST00000370549.5 | c.457C>T | p.Arg153Ter | stop_gained | 3/11 | 1 | |||
HPSE2 | ENST00000628193.2 | c.448+87957C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250432Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135402
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1461090Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726840
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 07, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89). This premature translational stop signal has been observed in individual(s) with clinical features of urofacial syndrome (PMID: 20560210, 27151922). This variant is present in population databases (rs267606865, gnomAD 0.005%). This sequence change creates a premature translational stop signal (p.Arg153*) in the HPSE2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HPSE2 are known to be pathogenic (PMID: 20560210, 25510506). - |
Congenital anomaly of kidney and urinary tract Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Aug 24, 2018 | - - |
Urofacial syndrome type 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 11, 2010 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at