Submissions for variant NM_018418.5(SPATA7):c.322C>T (p.Arg108Ter)

gnomAD frequency: 0.00006  dbSNP: rs80044281

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000358776	SCV000389301	likely pathogenic	SPATA7-Related Disorders	2017-04-28	criteria provided, single submitter	clinical testing	The SPATA7 c.322C>T (p.Arg108Ter) variant is stop-gained variant predicted to result in premature termination of the protein. The p.Arg108Ter variant has been reported in four studies in which it was identified in a total of seven patients with Leber congenital amaurosis, including four homozygotes and one compound heterozygote, and two compound heterozygotes with autosomal recessive retinitis pigmentosa (Wang et al. 2009; Perrault et al. 2010; Neveling et al. 2012; Xu et al. 2014). The variant was also found in a heterozygous state in six unaffected family members of patients. The variant was absent from at least 150 control individuals but is reported at a frequency of 0.00005 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence, the p.Arg108Ter variant is classified as pathogenic for SPATA7-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000001460	SCV001573419	pathogenic	Leber congenital amaurosis 3	2021-04-08	criteria provided, single submitter	research	The SPATA7 c.322C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP1. Based on this evidence we have classified this variant as Pathogenic.
Invitae	RCV000001460	SCV003443443	pathogenic	Leber congenital amaurosis 3	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg108*) in the SPATA7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPATA7 are known to be pathogenic (PMID: 19268277, 22334370, 23847139, 26047050, 26261414). This variant is present in population databases (rs80044281, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis or retinitis pigmentosa (PMID: 19268277, 22334370). ClinVar contains an entry for this variant (Variation ID: 1395). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987304	SCV004804470	pathogenic	Leber congenital amaurosis	2024-01-11	criteria provided, single submitter	clinical testing	Variant summary: SPATA7 c.322C>T (p.Arg108X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 3.2e-05 in 250260 control chromosomes (gnomAD). c.322C>T has been reported in the literature in individuals affected with Leber Congenital Amaurosis (e.g. Xiao_2019). The following publication has been ascertained in the context of this evaluation (PMID: 31908400). ClinVar contains an entry for this variant (Variation ID: 1395). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM	RCV000001460	SCV000021615	pathogenic	Leber congenital amaurosis 3	2009-03-01	no assertion criteria provided	literature only
GeneReviews	RCV000001460	SCV000086979	not provided	Leber congenital amaurosis 3		no assertion provided	literature only
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV000001460	SCV001432529	pathogenic	Leber congenital amaurosis 3		no assertion criteria provided	research
Clinical Genetics, Academic Medical Center	RCV001699098	SCV001922731	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699098	SCV001953582	pathogenic	not provided		no assertion criteria provided	clinical testing