NM_021828.5(HPSE2):c.1465_1466del (p.Asn489fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 18, 2023
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:: RCV001241819.4

Allele description

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]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001414867	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20560209, 20560210, 28492532
SCV004167718	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 18, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001414867

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 21, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004167718

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Oct 18, 2023)

germline

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	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Mutations in HPSE2 cause urofacial syndrome.

Daly SB, Urquhart JE, Hilton E, McKenzie EA, Kammerer RA, Lewis M, Kerr B, Stuart H, Donnai D, Long DA, Burgu B, Aydogdu O, Derbent M, Garcia-Minaur S, Reardon W, Gener B, Shalev S, Smith R, Woolf AS, Black GC, Newman WG.

Am J Hum Genet. 2010 Jun 11;86(6):963-9. Erratum in: Am J Hum Genet. 2010 Aug 13;87(2):309.

PubMed [citation]

PMID:: 20560210
PMCID:: PMC3032078

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001414867.3

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

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 84). This premature translational stop signal has been observed in individuals with urofacial syndrome (PMID: 20560209, 20560210). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs397515338, gnomAD 0.03%). This sequence change creates a premature translational stop signal (p.Asn489Profs*126) in the HPSE2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 104 amino acid(s) of the HPSE2 protein.

#	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 GeneDx, SCV004167718.1

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

Description

Frameshift variant predicted to result in the deletion of the last 104 amino acids, replaced with 125 incorrect amino acids; This variant is associated with the following publications: (PMID: 20560209, 11446407, 31589614, 35812751, 20560210)

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

Last Updated: Mar 16, 2024

ClinVar

Relating variation to medicine