Submissions for variant NM_003072.5(SMARCA4):c.223-7C>G

gnomAD frequency: 0.00003  dbSNP: rs762146990

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000234285	SCV000286011	likely benign	Rhabdoid tumor predisposition syndrome 2	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000417528	SCV000532553	likely benign	not specified	2016-10-07	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV001126400	SCV001285591	benign	Coffin-Siris syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV001726062	SCV001961768	likely benign	not provided	2021-11-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001808604	SCV002057025	likely benign	Intellectual disability, autosomal dominant 16	2021-07-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001726062	SCV004220404	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing	To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00012 (16/128962 chromosomes in European (Non-Finnish) subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant may affect proper SMARCA4 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.