NM_000202.8(IDS):c.1504T>A (p.Trp502Arg) AND Mucopolysaccharidosis, MPS-II

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 6, 2022
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:: RCV002830000.2

Allele description

NM_000202.8(IDS):c.1504T>A (p.Trp502Arg)

Gene:

IDS:iduronate 2-sulfatase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000202.8(IDS):c.1504T>A (p.Trp502Arg)

HGVS:

NC_000023.11:g.149482895A>T
NG_011900.3:g.27440T>A
NM_000202.8:c.1504T>AMANE SELECT
NM_001166550.4:c.1234T>A
NP_000193.1:p.Trp502Arg
NP_001160022.1:p.Trp412Arg
NC_000023.10:g.148564426A>T

Protein change:

W412R

Molecular consequence:

NM_000202.8:c.1504T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001166550.4:c.1234T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-II (MPS2)
Synonyms:: Mucopolysaccharidosis type II; Attenuated MPS (subtype; formerly known as mild MPS II); Severe MPS II; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010674; MedGen: C0026705; Orphanet: 580; OMIM: 309900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003214691	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 6, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1639384, 22976768, 35144014, 35242576, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003214691

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 6, 2022)

germline

clinical testing

PubMed (5)
[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

Detection of point mutations and a gross deletion in six Hunter syndrome patients.

Flomen RH, Green PM, Bentley DR, Giannelli F, Green EP.

Genomics. 1992 Jul;13(3):543-50.

PubMed [citation]

PMID:: 1639384

Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations.

Pollard LM, Jones JR, Wood TC.

J Inherit Metab Dis. 2013 Mar;36(2):179-87. doi: 10.1007/s10545-012-9533-7. Epub 2012 Sep 14.

PubMed [citation]

PMID:: 22976768

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003214691.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 502 of the IDS protein (p.Trp502Arg). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Trp502 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 1639384, 22976768, 35144014, 35242576), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IDS protein function. This variant has not been reported in the literature in individuals affected with IDS-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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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