ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.883G>A (p.Gly295Ser) (rs199476349)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000058985 SCV000110815 pathogenic not provided 2013-02-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000150060 SCV000439436 likely pathogenic Metachromatic leukodystrophy 2017-04-27 criteria provided, single submitter clinical testing The ARSA c.883G>A (p.Gly295Ser) variant (previously reported as c.887G>A, p.Gly293Ser) has been reported in two studies in which it was found in a compound heterozygous state with a second missense variant in a total of three individuals with metachromatic leukodystrophy (Berna et al. 2004; Biffi et al. 2008). One of the compound heterozygous individuals was also heterozygous for two additional variants (one known phenotype modifier and one functional polymorphism known to reduce enzyme activity) but did not carry the most common pseudodeficiency alleles (Biffi et al. 2008). Control data are unavailable for this variant, which is reported at a frequency of 0.00003 in the European (non-Finnish) population of the Exome Aggregation Consortium. However, this frequency is based on two alleles only in a region of good sequence coverage, suggesting the variant is rare. The p.Gly295Ser variant is located in a conserved residue in a functionally important domain of the protein. Functional studies in BHK-21 cells demonstrated the variant to be a null allele, causing the complete loss of enzyme activity (Berna et al. 2004). Based on the evidence, the p.Gly295Ser variant is classified as likely pathogenic for arylsulfatase A deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Counsyl RCV000150060 SCV000486786 likely pathogenic Metachromatic leukodystrophy 2016-08-09 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000058985 SCV000090506 not provided not provided no assertion provided not provided

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