VCV000426817.14 - ClinVar

NM_000203.5(IDUA):c.667G>A (p.Asp223Asn)

Germline

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.

(6)

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.

Benign/Likely benign; other

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000203.5(IDUA):c.667G>A (p.Asp223Asn)

Variation ID: 426817 Accession: VCV000426817.14

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4p16.3 4: 1001756 (GRCh38) [ NCBI UCSC ] 4: 995544 (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	May 22, 2017	May 1, 2024	Nov 19, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_000203.5:c.667G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000194.2:p.Asp223Asn	missense
NM_001363576.1:c.271G>A	NP_001350505.1:p.Asp91Asn	missense
NR_110313.1:n.755G>A		non-coding transcript variant
NC_000004.12:g.1001756G>A
NC_000004.11:g.995544G>A
NG_008103.1:g.19760G>A
LRG_1277:g.19760G>A
LRG_1277t1:c.667G>A	LRG_1277p1:p.Asp223Asn

... more HGVS ... less HGVS

Protein change

D223N, D91N

Other names

Canonical SPDI

NC_000004.12:1001755:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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.

0.00260 (A)

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

The Genome Aggregation Database (gnomAD), exomes 0.00036

Exome Aggregation Consortium (ExAC) 0.00058

The Genome Aggregation Database (gnomAD) 0.00166

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00179

Trans-Omics for Precision Medicine (TOPMed) 0.00201

1000 Genomes Project 0.00260

1000 Genomes Project 30x 0.00312

Links

ClinGen: CA2802050 dbSNP: rs183347428 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.
IDUA		-	-	GRCh38 GRCh37	1391	2155

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 type 1	other (3)	criteria provided, single submitter	Dec 19, 2018	RCV000708550.14
not provided	Benign (2)	criteria provided, single submitter	Sep 28, 2018	RCV000675603.14
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Nov 19, 2021	RCV002527033.9

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.	More information 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.
other pseudodeficiency allele (Dec 19, 2018)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Mucopolysaccharidosis type I Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000837661.2 First in ClinVar: Oct 10, 2018 Last updated: Aug 14, 2019	Publications: PubMed (1) PubMed: 28492532
Benign (Sep 28, 2018)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000577361.4 First in ClinVar: May 22, 2017 Last updated: Sep 26, 2021	Comment: This variant is associated with the following publications: (PMID: 27939258, 27238910)
Likely benign (Nov 19, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV003632591.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Uncertain significance (May 16, 2017)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801300.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Benign (Apr 23, 2020)	no assertion criteria provided Method: clinical testing	Mucopolysaccharidosis type I Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001457277.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
not provided (-)	no classification provided Method: literature only	Mucopolysaccharidosis type 1 Affected status: unknown Allele origin: germline	GeneReviews Accession: SCV002016348.2 First in ClinVar: Nov 20, 2021 Last updated: Oct 01, 2022	Publications: BookShelf: NBK1162 BookShelf: NBK1162 Comment: Pseudodeficiency variants

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mucopolysaccharidosis Type I.	Adam MP	-	2024	PMID: 20301341

Text-mined citations for rs183347428 ...

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 Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000203.5(IDUA):c.667G>A (p.Asp223Asn)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs183347428 ...