Submissions for variant NM_001130438.3(SPTAN1):c.1806+4A>G

gnomAD frequency: 0.00005  dbSNP: rs770046688

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000726972	SCV000243075	likely benign	not provided	2020-07-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081620	SCV000562971	likely benign	Early infantile epileptic encephalopathy with suppression bursts	2024-12-17	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000726972	SCV000704582	uncertain significance	not provided	2017-01-09	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001781557	SCV002025598	uncertain significance	Developmental and epileptic encephalopathy, 5	2020-04-26	criteria provided, single submitter	clinical testing	The inherited c.1806+4A>G splice-region variant is located in intron14 (of 56) of the SPTAN1 gene and is predicted by multiple In Silico tools to alter normal mRNA splicing. This variant has not been reported in the affected individuals in the literature. The variant has been reported in ClinVar (Variation ID: 207265). The variant has 0.0002315 allele frequency in the gnomAD database across all populations (58 out of 250,568 heterozygous alleles) and 0.00159 allele frequency in Latino subpopulation represented in gnomAD (55 out of 34,578 heterozygous alleles). The c.1806+4A>G variant affects a moderately conserved nucleotide. Functional studies are required to evaluate the potential pathogenicity of this variant. Based on the available evidence, the inherited c.1806+4A>G splice-region variant in the SPTAN1 gene is assessed as a variant of uncertain significance.
Genome-Nilou Lab	RCV001781557	SCV002056538	benign	Developmental and epileptic encephalopathy, 5	2021-07-15	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001781557	SCV002495975	uncertain significance	Developmental and epileptic encephalopathy, 5	2021-08-31	criteria provided, single submitter	clinical testing	SPTAN1 NM_001130438.2 intron 14 c.1806+4A>G: This variant has not been reported in the literature but is present in 0.2% (55/34578) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-131345132-A-G?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:207265). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Splice prediction tools suggest that this variant may alter splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.