ClinVar Miner

Submissions for variant NM_019066.5(MAGEL2):c.1996dup (p.Gln666fs) (rs770374710)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000380351 SCV000329409 pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing The c.1996dupC variant in the MAGEL2 gene has been reported previously, often de novo, in multiple unrelated individuals with Schaaf-Yang syndrome, formerly called Prader-Willi-like syndrome (Soden et al., 2014; Fountain et al., 2016; Palomares-Bralo et al., 2017). This variant was also reported in a large family with multiple individuals exhibiting features of Schaaf-Yang syndrome, all of whom inherited the variant from their father due to imprinting effects in the MAGEL2 gene (Aten et al., 2016). The c.1996dupC variant causes a frameshift starting with codon Glutamine 666, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 47 of the new reading frame, denoted p.Gln666ProfsX47. This variant causes the deletion of the final 584 amino acids, insertion of 46 incorrect residues, and is predicted to cause loss of normal protein function through protein truncation. The c.1996dupC variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1996dupC as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000380351 SCV000703044 pathogenic not provided 2016-11-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000622753 SCV000740854 pathogenic Inborn genetic diseases 2015-03-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Undiagnosed Diseases Network,NIH RCV000170356 SCV000746657 pathogenic Schaaf-yang syndrome 2017-05-12 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000170356 SCV000928360 pathogenic Schaaf-yang syndrome 2018-07-10 criteria provided, single submitter clinical testing PVS1, PS2, PP5
OMIM RCV000170356 SCV000222765 pathogenic Schaaf-yang syndrome 2014-12-03 no assertion criteria provided literature only
Department of Pediatrics and Neonatology,Nagoya City University Graduate School of Medical Sciences RCV000170356 SCV000784669 pathogenic Schaaf-yang syndrome 2018-06-25 no assertion criteria provided clinical testing

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