Submissions for variant NM_006642.5(SDCCAG8):c.567G>A (p.Trp189Ter)

dbSNP: rs797045948

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194004	SCV000248835	pathogenic	Senior-Loken syndrome 7	2015-07-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001731515	SCV001983610	likely pathogenic	Bardet-Biedl syndrome	2021-09-21	criteria provided, single submitter	clinical testing	Variant summary: SDCCAG8 c.567G>A (p.Trp189X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay. Truncations downstream of this position have been reported in HGMD in association with Bardet-Biedl Syndrome. The variant was absent in 251464 control chromosomes. To our knowledge, no occurrence of c.567G>A in individuals affected with Bardet-Biedl Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002517977	SCV003278911	pathogenic	Senior-Loken syndrome 7; Bardet-Biedl syndrome 16	2022-10-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 212141). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp189*) in the SDCCAG8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDCCAG8 are known to be pathogenic (PMID: 20835237, 22190896).
PreventionGenetics, part of Exact Sciences	RCV004530147	SCV004709026	likely pathogenic	SDCCAG8-related disorder	2024-01-18	criteria provided, single submitter	clinical testing	The SDCCAG8 c.567G>A variant is predicted to result in premature protein termination (p.Trp189*). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Nonsense variants in SDCCAG8 are expected to be pathogenic. This variant is interpreted as likely pathogenic.