Submissions for variant NM_005633.4(SOS1):c.2964+17A>G

gnomAD frequency: 0.00018  dbSNP: rs201906525

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000418437	SCV000514727	benign	not specified	2015-05-01	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000418437	SCV001339237	benign	not specified	2020-03-23	criteria provided, single submitter	clinical testing	Variant summary: SOS1 c.2964+17A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00032 in 250042 control chromosomes, predominantly at a frequency of 0.0035 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is significantly above the estimated maximal expected allele frequency for a pathogenic variant in SOS1 causing Noonan Syndrome and Related Conditions phenotype (3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.2964+17A>G in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002061522	SCV002485291	benign	RASopathy	2024-01-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467780	SCV002763255	benign	Noonan syndrome 4		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002467779	SCV002763256	benign	Fibromatosis, gingival, 1		criteria provided, single submitter	clinical testing