VCV002138749.6 - ClinVar

NM_000202.8(IDS):c.880-2A>C

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (2)

2 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000202.8(IDS):c.880-2A>C

Variation ID: 2138749 Accession: VCV002138749.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq28 X: 149490442 (GRCh38) [ NCBI UCSC ] X: 148571973 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 8, 2023	Feb 15, 2026	Jun 7, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000202.8:c.880-2A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor
NM_001166550.4:c.610-2A>C		splice acceptor
NM_006123.5:c.880-2A>C		splice acceptor
NC_000023.11:g.149490442T>G
NC_000023.10:g.148571973T>G
NG_011900.3:g.19893A>C
NG_042264.2:g.3798T>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000023.11:149490441:T:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA414520575 dbSNP: rs2520813902 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
IDS		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	744	1768
LOC106050102	-	-	-	GRCh38	-	843

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Mucopolysaccharidosis, MPS-II	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jun 7, 2024	RCV003066393.7

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jun 07, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Mucopolysaccharidosis, MPS-II	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova Accession: SCV005089288.2 First in ClinVar: Aug 04, 2024 Last updated: Apr 13, 2025 Comment: Classification method: ACMG Guidelines [PMID:25741868] with modifications	Publications: PubMed (1) PubMed: 22976768 Comment: show Null variant (PVS1_VeryStrong), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Patient’s phenotype or family history highly specific for the disease (PP4_Strong) (less) Observation: 1 Collection method: literature only Allele origin: germline Affected status: yes more Observation 1 Collection method: literature only Allele origin: germline Affected status: yes Number of individuals with the variant: 1 Sex: male

Pathogenic (Oct 04, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Mucopolysaccharidosis, MPS-II	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003445271.4 First in ClinVar: Feb 07, 2023 Last updated: Feb 15, 2026	Publications: PubMed (5) PubMed: 16199547‚ 22976768‚ 33676511‚ 8940265‚ 9875019 Comment: show For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with clinical features of mucopolysaccharidosis II (PMID: 22976768, 33676511). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the IDS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IDS are known to be pathogenic (PMID: 8940265, 9875019). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with clinical features of mucopolysaccharidosis II (PMID: 22976768, 33676511). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 6 of the IDS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IDS are known to be pathogenic (PMID: 8940265, 9875019).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Analysis of long-term observations of the large group of Russian patients with Hunter syndrome (mucopolysaccharidosis type II).	Semyachkina AN	BMC medical genomics	2021	PMID: 33676511
Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations.	Pollard LM	Journal of inherited metabolic disease	2013	PMID: 22976768
Splicing in action: assessing disease causing sequence changes.	Baralle D	Journal of medical genetics	2005	PMID: 16199547
Mutation analysis in 57 unrelated patients with MPS II (Hunter's disease).	Vafiadaki E	Archives of disease in childhood	1998	PMID: 9875019
Mucopolysaccharidosis type II (Hunter syndrome): mutation "hot spots" in the iduronate-2-sulfatase gene.	Rathmann M	American journal of human genetics	1996	PMID: 8940265

Text-mined citations for rs2520813902 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026