ClinVar Miner

Submissions for variant NM_016038.2(SBDS):c.183_184delTAinsCT (p.Lys62Ter) (rs113993991)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255938 SCV000321933 pathogenic not provided 2017-10-23 criteria provided, single submitter clinical testing The pathogenic variant c.183_184delTAinsCT introduces a premature stop codon in place of amino acid Lys62 and is predicted to cause loss of normal protein function either through protein truncation or nonsense mediated mRNA decay. Functional studies suggest that truncating variants may affect the protein's cellular localization and motility (Austin et al., 2005; Orelio et al., 2011).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000255938 SCV000338913 pathogenic not provided 2016-01-08 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000003346 SCV000596927 pathogenic Shwachman-Diamond syndrome 1 2016-10-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000622680 SCV000740931 pathogenic Inborn genetic diseases 2014-06-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000003346 SCV000967682 pathogenic Shwachman-Diamond syndrome 1 2018-12-04 criteria provided, single submitter clinical testing The p.Lys62X variant in SBDS is the most common pathogenic variant identified in individuals with Shwachman-Diamond syndrome (Boocock 2003). It has also been id entified in 0.04% (9/19936) of East Asian chromosomes by gnomAD (http://gnomad.b roadinstitute.org); however, this allele frequency may not be accurate due to th e presence of a pseudogene (SBDSP). This variant usually occurs as the result of a gene conversion event and results in the introduction of a premature terminat ion codon at position 62. This alteration is then predicted to lead to a truncat ed or absent protein. Loss of function of the SBDS gene is an established diseas e mechanism in Shwachman-Diamond syndrome. In summary, this variant meets criter ia to be classified as pathogenic for autosomal recessive Shwachman-Diamond synd rome. PVS1, PM3_Very Strong.
OMIM RCV000003346 SCV000023504 pathogenic Shwachman-Diamond syndrome 1 2005-07-01 no assertion criteria provided literature only
GeneReviews RCV000003346 SCV000041300 pathologic Shwachman-Diamond syndrome 1 2008-07-17 no assertion criteria provided curation Converted during submission to Pathogenic.

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