Submissions for variant NM_006642.5(SDCCAG8):c.252del (p.Ala85fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002720132	SCV002992646	pathogenic	Senior-Loken syndrome 7; Bardet-Biedl syndrome 16	2025-01-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala85Glnfs*18) 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). This variant is present in population databases (rs766013756, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 1955937). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004534169	SCV004714071	uncertain significance	SDCCAG8-related disorder	2023-10-26	no assertion criteria provided	clinical testing	The SDCCAG8 c.252delA variant is predicted to result in a frameshift and premature protein termination (p.Ala85Glnfs*18). To our knowledge, this variant has not been reported in the literature. Although other protein truncating variants have been reported in the SDCCAG8 gene to be pathogenic, all of these variants are located downstream of the c.252del variant (Human Gene Mutation Database). This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-243434309-CA-C). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.