Submissions for variant NM_006939.4(SOS2):c.213+18A>T

gnomAD frequency: 0.00096  dbSNP: rs143888968

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589583	SCV000698739	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.213+18A>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts the creation of an SRp40 ESE site at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 163/120530 control chromosomes from all ethnicities, but is predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.00228 (151/66228). This frequency is about 912 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. To our knowledge, the variant of interest has not been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV000602142	SCV000714910	benign	not specified	2017-07-03	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002065136	SCV002380176	benign	Noonan syndrome 9	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002065136	SCV002763149	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV002065136	SCV003800540	benign	Noonan syndrome 9	2023-08-11	criteria provided, single submitter	clinical testing