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NM_000202.8(IDS):c.785T>A (p.Val262Glu) AND Mucopolysaccharidosis, MPS-II

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 1, 2023
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:
RCV001981569.7

Allele description [Variation Report for NM_000202.8(IDS):c.785T>A (p.Val262Glu)]

NM_000202.8(IDS):c.785T>A (p.Val262Glu)

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.785T>A (p.Val262Glu)
HGVS:
  • NC_000023.11:g.149496440A>T
  • NG_011900.3:g.13895T>A
  • NG_042264.2:g.9796A>T
  • NM_000202.8:c.785T>AMANE SELECT
  • NM_001166550.4:c.515T>A
  • NM_006123.5:c.785T>A
  • NP_000193.1:p.Val262Glu
  • NP_001160022.1:p.Val172Glu
  • NP_006114.1:p.Val262Glu
  • NC_000023.10:g.148577971A>T
  • NG_042264.1:g.9795A>T
  • NR_104128.2:n.954T>A
Protein change:
V172E
Links:
dbSNP: rs782053689
NCBI 1000 Genomes Browser:
rs782053689
Molecular consequence:
  • NM_000202.8:c.785T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001166550.4:c.515T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006123.5:c.785T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104128.2:n.954T>A - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002222558Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 1, 2023) 		germlineclinical testing

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

SCV004235544Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jul 13, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Invitae, SCV002222558.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IDS protein function. ClinVar contains an entry for this variant (Variation ID: 1443998). This variant has not been reported in the literature in individuals affected with IDS-related conditions. This variant is present in population databases (rs782053689, gnomAD 0.001%), including at least one homozygous and/or hemizygous individual. This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 262 of the IDS protein (p.Val262Glu).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Revvity Omics, Revvity, SCV004235544.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 16, 2024