NM_000203.5(IDUA):c.806C>G (p.Ser269Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 15, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001375619.1

Allele description [Variation Report for NM_000203.5(IDUA):c.806C>G (p.Ser269Cys)]

NM_000203.5(IDUA):c.806C>G (p.Ser269Cys)

Gene:

IDUA:alpha-L-iduronidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000203.5(IDUA):c.806C>G (p.Ser269Cys)

HGVS:

NC_000004.12:g.1001995C>G
NG_008103.1:g.19999C>G
NM_000203.5:c.806C>GMANE SELECT
NM_001363576.1:c.410C>G
NP_000194.2:p.Ser269Cys
NP_001350505.1:p.Ser137Cys
LRG_1277t1:c.806C>G
LRG_1277:g.19999C>G
LRG_1277p1:p.Ser269Cys
NC_000004.11:g.995783C>G
NC_000004.11:g.995783C>G
NM_000203.3:c.806C>G
NM_000203.4:c.806C>G
NR_110313.1:n.894C>G

Protein change:

S137C

Links:

dbSNP: rs202051939

NCBI 1000 Genomes Browser:

rs202051939

Molecular consequence:

NM_000203.5:c.806C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363576.1:c.410C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_110313.1:n.894C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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ectodermalneural cortex 1-like protein, partial [Ameca splendens]
ectodermalneural cortex 1-like protein, partial [Ameca splendens]
gi|1357622093|gb|AVL95403.1|

Protein
NO synthase
NO synthase
gi|742990|prf||2011304A

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001572540	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 15, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28676128, 33686258, 31341245 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001572540

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 15, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Phenotype prediction for mucopolysaccharidosis type I by in silico analysis.

Ou L, Przybilla MJ, Whitley CB.

Orphanet J Rare Dis. 2017 Jul 4;12(1):125. doi: 10.1186/s13023-017-0678-1.

PubMed [citation]

PMID:: 28676128
PMCID:: PMC5496269

High diagnosis rate for nonimmune hydrops fetalis with prenatal clinical exome from the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study.

Al-Kouatly HB, Makhamreh MM, Rice SM, Smith K, Harman C, Quinn A, Valcarcel BN, Firman B, Liu R, Hegde M, Critchlow E, Berger SI.

Genet Med. 2021 Jul;23(7):1325-1333. doi: 10.1038/s41436-021-01121-0. Epub 2021 Mar 8.

PubMed [citation]

PMID:: 33686258

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001572540.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: IDUA c.806C>G (p.Ser269Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00037 in 203588 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in IDUA causing Mucopolysaccharidosis Type 1 (0.00037 vs 0.0027), allowing no conclusion about variant significance. c.806C>G has been reported in the literature in compound heterozygosity with IDUA c.757G>T (p.Gly253Cys) in a prenatal case of Nonimmune hydrops fetalis. A homozygous occurrence of SUMF1 c.691dupT (p.Trp231LeufsX11) was also detected in this case which was diagnostic for multiple sulfatase deficiency (Al-Kouatly_2021). This report does not provide unequivocal conclusions about association of the variant with Mucopolysaccharidosis Type 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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