ClinVar Genomic variation as it relates to human health
NM_000202.8(IDS):c.121_123del (p.Leu41del)
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.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000202.8(IDS):c.121_123del (p.Leu41del)
Variation ID: 1065310 Accession: VCV001065310.2
- Type and length
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Deletion, 3 bp
- Location
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Cytogenetic: Xq28 X: 149504274-149504276 (GRCh38) [ NCBI UCSC ] X: 148585804-148585806 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 May 1, 2021 Aug 4, 2024 Jun 7, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000202.8:c.121_123del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000193.1:p.Leu41del inframe deletion NM_000202.8:c.121_123delCTC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001166550.4:c.-106_-104del 5 prime UTR NM_006123.5:c.121_123del NP_006114.1:p.Leu41del inframe deletion NR_104128.2:n.290_292del non-coding transcript variant NC_000023.11:g.149504274_149504276del NC_000023.10:g.148585804_148585806del NG_011900.3:g.6059_6061del - Protein change
- L41del
- Other names
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- Canonical SPDI
- NC_000023.11:149504273:GAG:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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IDS | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
660 | 1573 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jun 7, 2024 | RCV001375841.4 |
Submissions - Germline
Classification
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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
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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
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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. |
More information
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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. |
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Mucopolysaccharidosis, MPS-II
(X-linked inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004048019.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The inframe deletion variant p.R4Q in LIPA (NM_000235.4) in IDS gene has been submitted to ClinVar as Likely Pathogenic, but no details are available for … (more)
The inframe deletion variant p.R4Q in LIPA (NM_000235.4) in IDS gene has been submitted to ClinVar as Likely Pathogenic, but no details are available for independent assessment. It has not been reported in affected individuals. The p.Leu41del variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This p.Leu41del causes deletion of amino acid Leucine at position 41. Since this inframe deletion/insertion is not expected to cause protein truncation, the above variant has been classified as Variant of Uncertain Significance (VUS). (less)
Clinical Features:
Nephrotic syndrome (present)
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Pathogenic
(Jun 07, 2024)
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criteria provided, single submitter
Method: literature only
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Mucopolysaccharidosis, MPS-II
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova
Accession: SCV005089166.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024
Comment:
Classification method: ACMG Guidelines [PMID:25741868] with modifications
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Comment:
Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Moderate), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Protein … (more)
Prevalence of the variant significantly increased in affected individuals compared with controls (PS4_Moderate), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Protein length changes in a nonrepeat region or stop–loss variants (PM4_Strong), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate) (less)
Number of individuals with the variant: 10
Sex: male
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Likely pathogenic
(May 01, 2014)
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no assertion criteria provided
Method: research
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Mucopolysaccharidosis, MPS-II
(X-linked recessive inheritance)
Affected status: yes
Allele origin:
germline
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Pediatrics, All India Institute of Medical Sciences, New Delhi
Accession: SCV001572613.1
First in ClinVar: May 01, 2021 Last updated: May 01, 2021 |
Comment:
The variant c.121_123delCTC (p.L41del) was found to be a small in-frame deletion, where the peptide sequence gets shortened by an aliphatic nonpolar neutral amino acid, … (more)
The variant c.121_123delCTC (p.L41del) was found to be a small in-frame deletion, where the peptide sequence gets shortened by an aliphatic nonpolar neutral amino acid, Leucine at 41 position. It was detected in the hemizygous condition in one of the patients with sever MPS-2 phenotype from Uttarpradesh state of India. (less)
Clinical Features:
Coarse facial features (present) , Arthropathy (present) , Macrocephaly (present) , Hepatosplenomegaly (present) , Delayed gross motor development (present) , Intellectual disability (present) , Hearing … (more)
Coarse facial features (present) , Arthropathy (present) , Macrocephaly (present) , Hepatosplenomegaly (present) , Delayed gross motor development (present) , Intellectual disability (present) , Hearing impairment (present) , Abnormal echocardiogram (present) (less)
Indication for testing: Hunter Syndrome
Age: 0-9 years
Sex: male
Ethnicity/Population group: INDIAN
Geographic origin: Uttarpradesh, India
Comment on evidence:
The variant c.121_123delCTC (p.L41del) was found to be a small in-frame deletion, where the peptide sequence gets shortened by an aliphatic nonpolar neutral amino acid, … (more)
The variant c.121_123delCTC (p.L41del) was found to be a small in-frame deletion, where the peptide sequence gets shortened by an aliphatic nonpolar neutral amino acid, Leucine at 41 position. It was detected in the hemizygous condition in one of the patients with sever MPS-2 phenotype from Uttarpradesh state of India. (less)
Method: Sanger sequencing was performed on ABI 3130 genetic analyser (Applied Biosystem, USA) capillary electrophoresis. Data was analysed by ABI sequence analysis (SeqScape version 2.5) software as well as manually by using software: Chromaspro (Version-1.7.5, Technilysium Pvt. Ltd, Australia) and FinchTV (Version 1.4.0, Geospiza, Perkinelmer, USA).
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Clinical characteristics and genotypes of 201 patients with mucopolysaccharidosis type II in China: A retrospective, observational study. | Zhong L | Clinical genetics | 2023 | PMID: 36945845 |
Genotype-phenotype spectrum of 130 unrelated Indian families with Mucopolysaccharidosis type II. | Agrawal N | European journal of medical genetics | 2022 | PMID: 35144014 |
Molecular characterization of a large cohort of mucopolysaccharidosis patients: Iran Mucopolysaccharidosis RE-diagnosis study (IMPRESsion). | Ghaffari SR | Human mutation | 2022 | PMID: 35005816 |
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 |
Genetic analysis of 63 Chinese patients with mucopolysaccharidosis type II: Functional characterization of seven novel IDS variants. | Zhang W | Clinica chimica acta; international journal of clinical chemistry | 2019 | PMID: 30639582 |
Genotype-phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II. | Dvorakova L | Clinical genetics | 2017 | PMID: 27883178 |
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 | Molecular genetics and metabolism | 2016 | PMID: 27246110 |
Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II. | Sohn YB | Clinical genetics | 2012 | PMID: 21291454 |
Mutational spectrum of the iduronate 2 sulfatase gene in 25 unrelated Korean Hunter syndrome patients: identification of 13 novel mutations. | Kim CH | Human mutation | 2003 | PMID: 12655569 |
Text-mined citations for rs2124066296 ...
HelpRecord last updated Aug 04, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.