ClinVar Miner

Submissions for variant NM_000512.5(GALNS):c.740G>A (p.Gly247Asp) (rs761385192)

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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 RCV000298139 SCV000331335 likely pathogenic not provided 2016-02-22 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826109 SCV000967617 likely pathogenic Morquio syndrome 2018-01-18 criteria provided, single submitter clinical testing VARIANT INTERPRETATION: The p.Gly247Asp (NM_000512.4 c.740G>A) variant in GALNS has been reported in at least 5 compound heterozygous patients with mucopolysacc haridosis type IVa (Bunge 1997, Tomatsu 2004, Bhattacharya 2014, and Morrone 201 4). This variant has also been identified in 6/126,672 of European chromosomes b y the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbS NP rs761385192). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, although additional studies are required to fully establish its clinical significance, the p.Gly247 Asp variant is likely pathogenic for mucopolysaccaridosis type IVa in an autosom al recessive manner based on its occurrence in affected individuals. ACMG/AMP Cr iteria applied: PM2, PM3 (upgraded to Strong based on multiple occurrences) (Ric hards 2015).
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV001544508 SCV001547783 likely pathogenic Mucopolysaccharidosis, MPS-IV-A 2021-02-01 criteria provided, single submitter research In vivo functional studies supportive of a damaging effect on the gene product (low to null enzymatic activity in homozygotes; PS3_supporting); the prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (PS4_strong); very low frequency in gnomAD v2.1.1 (PM2_moderate); multiple lines of computational evidence support a deleterious effect on the gene (PP3_supporting)
Nilou-Genome Lab RCV001544508 SCV001762419 likely benign Mucopolysaccharidosis, MPS-IV-A 2021-08-02 criteria provided, single submitter clinical testing We found this variant in a 40-year-old asymptomatic female in a homozygous state.

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