rs61736892
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM5BP4_StrongBS1_SupportingBS2
The NM_000202.8(IDS):c.641C>T(p.Thr214Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,210,141 control chromosomes in the GnomAD database, including 50 homozygotes. There are 819 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T214R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000202.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IDS | NM_000202.8 | c.641C>T | p.Thr214Met | missense_variant | 5/9 | ENST00000340855.11 | |
IDS | NM_001166550.4 | c.371C>T | p.Thr124Met | missense_variant | 5/9 | ||
IDS | NM_006123.5 | c.641C>T | p.Thr214Met | missense_variant | 5/8 | ||
IDS | NR_104128.2 | n.810C>T | non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IDS | ENST00000340855.11 | c.641C>T | p.Thr214Met | missense_variant | 5/9 | 1 | NM_000202.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0138 AC: 1551AN: 112191Hom.: 28 Cov.: 24 AF XY: 0.0124 AC XY: 427AN XY: 34377
GnomAD3 exomes AF: 0.00398 AC: 730AN: 183456Hom.: 17 AF XY: 0.00256 AC XY: 174AN XY: 67888
GnomAD4 exome AF: 0.00145 AC: 1596AN: 1097898Hom.: 22 Cov.: 30 AF XY: 0.00107 AC XY: 387AN XY: 363260
GnomAD4 genome ? AF: 0.0139 AC: 1555AN: 112243Hom.: 28 Cov.: 24 AF XY: 0.0125 AC XY: 432AN XY: 34439
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-II Pathogenic:2Benign:5
Likely pathogenic, criteria provided, single submitter | literature only | Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova | Jun 07, 2024 | Absent from controls (or at low frequency) in gnomAD database (PM2_Moderate), Missense change at the same amino acid residue as a pathogenic variant (PM5_Supporting), Missense variant in a gene with a low rate of benign missense variation (PP2_Supporting), Patient’s phenotype or family history highly specific for the disease (PP4_Moderate), Multiple lines of computational evidence suggest no impact on gene or gene product (BP4_Supporting) - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Pathogenic, criteria provided, single submitter | research | IIFP, CONICET-UNLP | Dec 07, 2010 | The patient with this genetic variant is hemizygous for the variant in IDS gene: c.641C>T It is an X-linked disorder The disorder is Hunter disease or mucopolysaccharidosis type II The patient has a deficient activity of Iduronate 2 sulfatase in dried blood filter paper test. And normal activity of another sulfatase ruling out multiple sulfatase deficiency. He had two other family members affected from the same disorder, from the maternal side: a maternal uncle and maternal grand uncle. Both have died because of Hunter disease. Clinical manifestations are: Cifosis, short neck, disostosis multiplex, coarse face, hernia, macroglosia, claw hand, hepatosplenomegaly - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Jan 02, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Nov 21, 2018 | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 08, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 26, 2017 | Variant summary: The IDS c.641C>T (p.Thr214Met) variant involves the alteration of a non-conserved nucleotide and 2/4 in silico tools predict a benign outcome for this variant. This variant was found in 444/87744 control chromosomes (12 homozygotes, 100 hemizygotes) at a frequency of 0.0050602, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic IDS variant (0.0028868), suggesting this variant is likely a benign polymorphism. A publication, Chkioua_2011, cites the variant in an affected individual, who was homozygous for the pathogenic R88P variant. This variant also co-occurred with a pathogenic variant, c.1402C>T (p.R468W) in a sample tested at our laboratory. In addition, multiple clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | This variant is associated with the following publications: (PMID: 21605424, 27884173, 27695081, 27896113, 31019283, 32448126) - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2014 | This alteration is classified as 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at