Submissions for variant NM_003072.5(SMARCA4):c.722_733del (p.229GP[6])

dbSNP: rs568390760

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000229477	SCV000286141	likely benign	Rhabdoid tumor predisposition syndrome 2	2024-01-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000122063	SCV000597193	likely benign	not specified	2016-07-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567903	SCV000663942	likely benign	Hereditary cancer-predisposing syndrome	2018-05-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001354804	SCV001764663	likely benign	not provided	2022-04-18	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Sema4, Sema4	RCV000567903	SCV002535227	likely benign	Hereditary cancer-predisposing syndrome	2021-11-22	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001354804	SCV004221248	benign	not provided	2022-11-29	criteria provided, single submitter	clinical testing
ITMI	RCV000122063	SCV000086274	not provided	not specified	2013-09-19	no assertion provided	reference population
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354804	SCV001549507	uncertain significance	not provided		no assertion criteria provided	clinical testing	The SMARCA4 p.Gly241_Pro244del variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs568390760) and in ClinVar (classified as likely benign by Genetic Services Laboratory University of Chicago and Ambry Genetics and as VUS by Invitae). The variant was identified in control databases in 27 of 166304 chromosomes at a frequency of 0.000162 (Genome Aggregation Database Feb 27, 2017). The variant was found in the following populations: African in 22 of 15130 chromosomes (freq: 0.001454), Other in 2 of 5186 chromosomes (freq: 0.000386) and Latino in 3 of 25264 chromosomes (freq: 0.000119), while the variant was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish) and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. This variant is an in-frame deletion resulting in the removal of codons 241 to 244 in a proline-glycine repeat region, however the impact of this alteration on the SMARCA4 protein function is not known. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.