NM_000181.4(GUSB):c.1809dup (p.Asn604fs) AND Mucopolysaccharidosis type 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 2, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003495893.1

Allele description [Variation Report for NM_000181.4(GUSB):c.1809dup (p.Asn604fs)]

NM_000181.4(GUSB):c.1809dup (p.Asn604fs)

Gene:

GUSB:glucuronidase beta [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7q11.21

Genomic location:

Preferred name:

NM_000181.4(GUSB):c.1809dup (p.Asn604fs)

HGVS:

NC_000007.14:g.65961047dup
NG_016197.1:g.26271dup
NG_051954.1:g.92949dup
NG_051954.2:g.100277dup
NM_000181.4:c.1809dupMANE SELECT
NM_001284290.2:c.1371dup
NM_001293104.2:c.1239dup
NM_001293105.2:c.1152dup
NP_000172.2:p.Asn604fs
NP_001271219.1:p.Asn458fs
NP_001280033.1:p.Asn414fs
NP_001280034.1:p.Asn385fs
NC_000007.13:g.65426030_65426031insC
NC_000007.13:g.65426034dup
NR_120531.2:n.1754dup

Protein change:

N385fs

Molecular consequence:

NM_000181.4:c.1809dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001284290.2:c.1371dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293104.2:c.1239dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001293105.2:c.1152dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_120531.2:n.1754dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Mucopolysaccharidosis type 7 (MPS7)
Synonyms:: MPS VII; Mucopolysaccharidosis type VII; MPS 7; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009662; MedGen: C0085132; Orphanet: 584; OMIM: 253220

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004319948	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 2, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7680524, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004319948

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 2, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Mutational analysis of a patient with mucopolysaccharidosis type VII, and identification of pseudogenes.

Shipley JM, Klinkenberg M, Wu BM, Bachinsky DR, Grubb JH, Sly WS.

Am J Hum Genet. 1993 Mar;52(3):517-26.

PubMed [citation]

PMID:: 7680524
PMCID:: PMC1682147

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004319948.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GUSB protein in which other variant(s) (p.Trp627Cys) have been determined to be pathogenic (PMID: 7680524). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with GUSB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn604Glufs*2) in the GUSB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the GUSB 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

Last Updated: Feb 20, 2024

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