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

Total submissions: 7

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.