NM_000202.8(IDS):c.328A>G (p.Arg110Gly) AND Mucopolysaccharidosis, MPS-II

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jun 7, 2024
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:: RCV001378371.6

Allele description [Variation Report for NM_000202.8(IDS):c.328A>G (p.Arg110Gly)]

NM_000202.8(IDS):c.328A>G (p.Arg110Gly)

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.328A>G (p.Arg110Gly)

HGVS:

NC_000023.11:g.149503402T>C
NG_011900.3:g.6933A>G
NM_000202.8:c.328A>GMANE SELECT
NM_001166550.4:c.58A>G
NM_006123.5:c.328A>G
NP_000193.1:p.Arg110Gly
NP_001160022.1:p.Arg20Gly
NP_006114.1:p.Arg110Gly
NC_000023.10:g.148584932T>C
NM_000202.4:c.328A>G
NR_104128.2:n.497A>G

Protein change:

R110G

Links:

dbSNP: rs2124063287

NCBI 1000 Genomes Browser:

rs2124063287

Molecular consequence:

NM_000202.8:c.328A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001166550.4:c.58A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006123.5:c.328A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_104128.2:n.497A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

Clear Turn Off Turn On

Profile neighbors for GEO Profiles (Select 131338860) (199)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 131330422) (20)
GEO Profiles
HES3 hes family bHLH transcription factor 3 [Homo sapiens]
HES3 hes family bHLH transcription factor 3 [Homo sapiens]
Gene ID:390992

Gene
Gene Links for GEO Profiles (Select 131320555) (1)
Gene
Hypoxia effect on von Hippel Lindau-overexpressing renal cell carcinoma cells
Hypoxia effect on von Hippel Lindau-overexpressing renal cell carcinoma cells
Accession: GDS5810

GEO DataSets

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
SCV001575923	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27246110, 30639582, 28492532
SCV005088992	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 7, 2024)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 30639582, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001575923

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 24, 2021)

germline

clinical testing

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

SCV005088992

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 7, 2024)

germline

literature only

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	yes	1	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular diagnosis of 65 families with mucopolysaccharidosis type II (Hunter syndrome) characterized by 16 novel mutations in the IDS gene: Genetic, pathological, and structural studies on iduronate-2-sulfatase.

Kosuga M, Mashima R, Hirakiyama A, Fuji N, Kumagai T, Seo JH, Nikaido M, Saito S, Ohno K, Sakuraba H, Okuyama T.

Mol Genet Metab. 2016 Jul;118(3):190-197. doi: 10.1016/j.ymgme.2016.05.003. Epub 2016 May 7.

PubMed [citation]

PMID:: 27246110

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001575923.4

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

Description

This variant is not present in population databases (ExAC no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg110 amino acid residue in IDS. Other variant(s) that disrupt this residue have been observed in individuals with IDS-related conditions (PMID: 27246110), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects IDS protein function (PMID: 30639582). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with mucopolysaccharidosis II (PMID: 30639582; Invitae). This sequence change replaces arginine with glycine at codon 110 of the IDS protein (p.Arg110Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.

#	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 Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV005088992.1

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

Description

In vitro or in vivo functional studies supportive of a damaging effect (PS3_Strong), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Strong)

#	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		1	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine