Submissions for variant NM_016038.4(SBDS):c.652C>T (p.Arg218Ter)

gnomAD frequency: 0.00001  dbSNP: rs113993998

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003125834	SCV003803166	likely pathogenic	not provided	2022-08-11	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation as the last 33 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 21695142, 29625052, 15776428, 15284109)
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315402	SCV004015289	likely pathogenic	Aplastic anemia	2023-07-07	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with a termination signal at codon 218 of the SBDS protein (p.Arg218Ter). Null variant (nonsense), in gene SBDS, for which loss-of-function is a known mechanism of disease (associated with Shwachman-Diamond syndrome 1 and Aplastic anemia. ClinVar classifies this variant as Pathogenic, rated 0 stars, no assertion criteria provided, with 1 submission, 1 publication (15284109). In-silico prediction models show pathogenic computational verdict based on 4 pathogenic predictions from BayesDel_addAF, DANN, FATHMM-MKL and MutationTaster vs 1 benign prediction from EIGEN. Therefore, this variant is classified as likely pathogenic.
Baylor Genetics	RCV003315402	SCV004202350	pathogenic	Aplastic anemia	2022-09-24	criteria provided, single submitter	clinical testing
GeneReviews	RCV000020735	SCV000041310	not provided	Shwachman-Diamond syndrome 1		no assertion provided	literature only