NM_000202.8(IDS):c.908C>T (p.Ser303Phe) 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:: RCV001564022.3

Allele description [Variation Report for NM_000202.8(IDS):c.908C>T (p.Ser303Phe)]

NM_000202.8(IDS):c.908C>T (p.Ser303Phe)

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.908C>T (p.Ser303Phe)

Other names:

p.Ser303Phe

HGVS:

NC_000023.11:g.149490412G>A
NG_011900.3:g.19923C>T
NG_042264.1:g.3767G>A
NM_000202.8:c.908C>TMANE SELECT
NM_001166550.4:c.638C>T
NM_006123.5:c.908C>T
NP_000193.1:p.Ser303Phe
NP_001160022.1:p.Ser213Phe
NP_006114.1:p.Ser303Phe
NC_000023.10:g.148571943G>A
NR_104128.2:n.1207C>T

Protein change:

S213F

Links:

dbSNP: rs2124020665

NCBI 1000 Genomes Browser:

rs2124020665

Molecular consequence:

NM_000202.8:c.908C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001166550.4:c.638C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006123.5:c.908C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104128.2:n.1207C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

Unknown function

Observations:

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001480192	Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002574932	Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 12, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005089303	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 (3) [See all records that cite these PMIDs] 35144014, 22976768, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001480192

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

maternal

clinical testing

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

SCV002574932

Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 12, 2022)

germline

clinical testing

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

SCV005089303

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 (3)
[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	3	not provided	not provided	not provided	not provided	literature only, clinical testing
Indian	maternal	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype spectrum of 130 unrelated Indian families with Mucopolysaccharidosis type II.

Agrawal N, Verma G, Saxena D, Kabra M, Gupta N, Mandal K, Moirangthem A, Sheth J, Puri RD, Bijarnia-Mahay S, Kapoor S, Danda S, H SV, Datar CA, Ranganath P, Shukla A, Dalal A, Srivastava P, Devi RR, Phadke SR.

Eur J Med Genet. 2022 Mar;65(3):104447. doi: 10.1016/j.ejmg.2022.104447. Epub 2022 Feb 8.

PubMed [citation]

PMID:: 35144014

Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations.

Pollard LM, Jones JR, Wood TC.

J Inherit Metab Dis. 2013 Mar;36(2):179-87. doi: 10.1007/s10545-012-9533-7. Epub 2012 Sep 14.

PubMed [citation]

PMID:: 22976768

See all PubMed Citations (3)

Details of each submission

From Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, SCV001480192.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Indian	1	not provided	not provided	clinical testing	PubMed (1)

#	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	not provided	not provided

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV002574932.1

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

Description

A hemizygous missense variant in exon 7 of the IDS gene that results in the amino acid substitution of Phenylalanine for Serine at codon 303 was detected. The observed variant c.908C>T (p.Ser303Phe) has not been reported in the 1000 genomes and gnomAD databases. The in silico prediction of the variant is disease causing by PROVEAN, SIFT and MutationTaster2. In summary, the variant meets our criteria to be classified as pathogenic.

#	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

From Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova, SCV005089303.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	literature only	PubMed (3)

Description

De novo (PS2_Moderate), Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Multiple lines of computational evidence support a deleterious effect (PP3_Supporting), 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		2	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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