ClinVar Miner

Submissions for variant NM_000203.5(IDUA):c.99T>G (p.His33Gln) (rs10794537)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078401 SCV000110247 benign not specified 2017-08-25 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078401 SCV000302986 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000337407 SCV000451732 benign Mucopolysaccharidosis type 1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000675598 SCV000976801 benign not provided 2018-04-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000337407 SCV001723455 benign Mucopolysaccharidosis type 1 2020-11-26 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001544423 SCV001763462 benign Hurler syndrome 2021-07-14 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001544424 SCV001763463 benign Mucopolysaccharidosis, MPS-I-H/S 2021-07-14 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001544425 SCV001763464 benign Mucopolysaccharidosis, MPS-I-S 2021-07-14 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000675598 SCV000801291 benign not provided 2015-10-23 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000078401 SCV001548626 benign not specified no assertion criteria provided clinical testing The IDUA p.His33Gln variant was identified in the literature as polymorphism/benign in studies of patients with Mucopolysaccharidosis type I (MPS I) disease (Chkioua_2011_21639919, Azab_2017_28649516, Atceken_2016_27511503, Lin_2013_24053568, Li_2002_12509712). The variant was also identified in the following databases: dbSNP (ID: rs10794537) as “With Benign Allele”, ClinVar (3x, as benign), Clinvitae database (3x as benign). This variant was identified in the 1000 Genomes Project in 4467 of 5008 chromosomes (frequency: 0.9), the genome Aggregation Database (beta, October 19th 2016) in 9303 (4255 homozygous) of 10182 chromosomes (freq. 0.9), the Exome Aggregation Consortium database (August 8th 2016) in 92436 (39108 homozygous) of 110100 chromosomes (freq. 0.83) in the following populations: African in 9151 of 9570 chromosomes (freq. 0.95), other in 2692 of 3248 chromosomes (freq. 0.82), Latino in 13176 of 16524 chromosomes (freq. 0.8), European non Finnish in 35257 of 44264 chromosomes (freq. 0.8), Ashkenazi Jewish in 6104 of 6814 chromosomes (freq. 0.9), east Asian in 3947 of 4612 chromosomes (freq. 0.85), Finnish in 6417 of 8150 chromosomes (freq. 0.8), and South Asian in 15692 of 16918 chromosomes (freq. 0.8), increasing the likelihood this is a high frequency benign variant, seen in all populations. The p.His33 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 4 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Human Genetics - Radboudumc,Radboudumc RCV000078401 SCV001953422 benign not specified no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000078401 SCV001978452 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000078401 SCV001979301 benign not specified no assertion criteria provided clinical testing

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