NM_000202.8(IDS):c.708+1G>A AND Mucopolysaccharidosis, MPS-II

Germline classification:: Pathogenic/Likely pathogenic (3 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:: RCV000204551.12

Allele description [Variation Report for NM_000202.8(IDS):c.708+1G>A]

NM_000202.8(IDS):c.708+1G>A

Genes:

LOC106050102:IDS recombination region [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.708+1G>A

HGVS:

NC_000023.11:g.149498106C>T
NG_011900.3:g.12229G>A
NG_042264.2:g.11462C>T
NM_000202.8:c.708+1G>AMANE SELECT
NM_001166550.4:c.438+1G>A
NM_006123.5:c.708+1G>A
NC_000023.10:g.148579637C>T
NM_000202.6:c.708+1G>A

Links:

dbSNP: rs864622778

Molecular consequence:

NM_000202.8:c.708+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001166550.4:c.438+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_006123.5:c.708+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-II (MPS2)
Synonyms:: Attenuated MPS (subtype; formerly known as mild MPS II); Severe MPS II; I2S deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010674; MedGen: C0026705; Orphanet: 580; OMIM: 309900

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
SCV000262539	IIFP, CONICET-UNLP	criteria provided, single submitter (ACMG Guidelines, 2007)	Pathogenic (Dec 7, 2011)	maternal	research	PubMed (1) [See all records that cite this PMID]
SCV002234986	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 7, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 27246110, 9875019, 31877959, 27896113, 28492532
SCV005089199	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 7, 2024)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 27896113, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000262539

IIFP, CONICET-UNLP

criteria provided, single submitter

(ACMG Guidelines, 2007)

Pathogenic
(Dec 7, 2011)

maternal

research

PubMed (1)
[See all records that cite this PMID]

SCV002234986

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 7, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV005089199

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely 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
not provided	maternal	yes	1	1	not provided	not provided	not provided	research

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee.

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

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

See all PubMed Citations (7)

Details of each submission

From IIFP, CONICET-UNLP, SCV000262539.3

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

Description

"exon loss" was previously submitted as the functional consequence for NM_000202.6:c.708+1G>A, but without providing the result of a functional assay.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002234986.5

#	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 affects a donor splice site in intron 5 of the IDS gene. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of mucopolysaccharidosis type II (PMID: 27896113, 27246110, 31877959, 9875019). ClinVar contains an entry for this variant (Variation ID: 221221). Experimental studies have shown that disruption of this splice site affects IDS protein function (PMID: 31877959). Studies have shown that this variant is associated with skipping of exon 5 but is expected to preserve the integrity of the reading frame (PMID: 27896113). For these reasons, this variant has been classified as Pathogenic.

#	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, SCV005089199.2

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

Description

Null variant (PVS1_Strong), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate)

#	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: Apr 12, 2026

ClinVar

Relating variation to medicine