Submissions for variant NM_006642.5(SDCCAG8):c.1120C>T (p.Arg374Ter)

dbSNP: rs770084716

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000785890	SCV000924466	likely pathogenic	Bardet-Biedl syndrome 16	2018-06-15	criteria provided, single submitter	research	The homozygous p.Arg374Ter variant was identified by our study in one individual with Bardet-Biedl syndrome. This variant has been identified in the literature in an affected homozygous Turkish proband with heterozygous unaffected parents (Schaefer et al. 2011). This variant has been identified in <0.01% (1/17226) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; rs770084716). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Loss of function of the SDCCAG8 gene is an established disease mechanism in autosomal recessive Bardet-Biedl Syndrome 16, and this is a loss of function variant. In summary, although additional studies are required to fully establish its pathogenicity, this variant is likely pathogenic.
3billion	RCV000785890	SCV002521239	pathogenic	Bardet-Biedl syndrome 16	2022-05-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Each parent is heterozygous for the variant. The variant has been reported to be associated with SDCCAG8 related disorder (ClinVar ID: VCV000635017). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
PreventionGenetics, part of Exact Sciences	RCV003413578	SCV004116285	pathogenic	SDCCAG8-related condition	2022-11-18	criteria provided, single submitter	clinical testing	The SDCCAG8 c.1120C>T variant is predicted to result in premature protein termination (p.Arg374*). This variant was reported in the homozygous state in an individual Bardet-Biedl syndrome 16 (Schaefer et al. 2010. PubMed ID: 22190896; Meyer et al. 2022. PubMed ID: 35112343). This variant is reported in 0.0055% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-243493893-C-T). Nonsense variants in SDCCAG8 are expected to be pathogenic. This variant is interpreted as pathogenic.