NM_021828.5(HPSE2):c.1465_1466del (p.Asn489fs) AND Urofacial syndrome type 1

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Dec 13, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000000104.22

Allele description [Variation Report for NM_021828.5(HPSE2):c.1465_1466del (p.Asn489fs)]

NM_021828.5(HPSE2):c.1465_1466del (p.Asn489fs)

Gene:

HPSE2:heparanase 2 (inactive) [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q24.2

Genomic location:

Preferred name:

NM_021828.5(HPSE2):c.1465_1466del (p.Asn489fs)

HGVS:

NC_000010.11:g.98490051_98490052del
NG_023416.1:g.750824_750825del
NM_001166244.1:c.1291_1292del
NM_001166245.1:c.1129_1130del
NM_001166246.1:c.1465_1466del
NM_021828.5:c.1465_1466delMANE SELECT
NP_001159716.1:p.Asn431fs
NP_001159717.1:p.Asn377fs
NP_001159718.1:p.Asn489fs
NP_068600.4:p.Asn489fs
NC_000010.10:g.100249808_100249809del
NM_021828.4:c.1465_1466del
NM_021828.4:c.1465_1466delAA

Protein change:

N377fs

Links:

OMIM: 613469.0002; dbSNP: rs397515338

NCBI 1000 Genomes Browser:

rs397515338

Molecular consequence:

NM_001166244.1:c.1291_1292del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001166245.1:c.1129_1130del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001166246.1:c.1465_1466del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021828.5:c.1465_1466del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Urofacial syndrome type 1
Identifiers:: MONDO: MONDO:0009368; MedGen: CN033872; Orphanet: 2704; OMIM: 236730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000020247	OMIM	no assertion criteria provided	Pathogenic (Jun 11, 2010)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 20560209, 11446407, 20560210
SCV000086986	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 20560209, 20560210
SCV000782663	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2017)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001752510	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002025028	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 11, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003935116	Eurofins-Biomnis	criteria provided, single submitter (Accession Criteria ClinVar Biomnis)	Likely pathogenic (Dec 13, 2022)	paternal	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	literature only, clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Three new European cases of urofacial (Ochoa) syndrome.

Garcia-Minaur S, Oliver F, Yanez JM, Soriano JR, Quinn F, Reardon W.

Clin Dysmorphol. 2001 Jul;10(3):165-70.

PubMed [citation]

PMID:: 11446407

Loss-of-function mutations in HPSE2 cause the autosomal recessive urofacial syndrome.

Pang J, Zhang S, Yang P, Hawkins-Lee B, Zhong J, Zhang Y, Ochoa B, Agundez JA, Voelckel MA, Fisher RB, Gu W, Xiong WC, Mei L, She JX, Wang CY.

Am J Hum Genet. 2010 Jun 11;86(6):957-62. Erratum in: Am J Hum Genet. 2010 Jul 9;87(1):161. Fisher, Richard B [added].

PubMed [citation]

PMID:: 20560209
PMCID:: PMC3032074

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000020247.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In affected individuals with urofacial syndrome (UFS1; 236730) from 2 United States pedigrees with a common Irish heritage, Pang et al. (2010) identified homozygosity for a 2-bp deletion (1465delAA) in exon 10 of the HPSE2 gene, predicted to cause a frameshift resulting in a larger protein of 613 amino acids with a completely different sequence for the last 125 residues.

In 2 Irish sisters with urofacial syndrome, originally reported by Garcia-Minaur et al. (2001), Daly et al. (2010) identified homozygosity for the 1465delAA mutation; Daly et al. (2010) predicted that the frameshift would result in nonsense-mediated decay or in a readily-degraded unfolded protein. The sisters had strikingly different presentations: one was severely affected from childhood and underwent multiple urologic surgeries, whereas the other was diagnosed only at age 25 years when she accompanied her sister to the urologic clinic. Their parents were heterozygous for the mutation, which was not found in 96 European controls.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV000086986.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV000782663.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV001752510.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002025028.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins-Biomnis, SCV003935116.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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