Submissions for variant NM_006939.4(SOS2):c.2162-4C>A

gnomAD frequency: 0.00961  dbSNP: rs57179949

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000590342	SCV000529312	benign	not provided	2017-01-04	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.
Invitae	RCV001084628	SCV000656014	benign	Noonan syndrome 9	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590342	SCV000698740	benign	not provided	2017-04-12	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.2162-4C>A variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 381/121160 control chromosomes from ExAC (including 4 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.033436 (347/10378). This frequency is about 13374 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 African origin. In addition, one clinical diagnostic laboratory in ClinVar has classified this variant as benign. The variant of interest has not, to our knowledge, been reported in literature. Taken together, this variant is classified as Benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813482	SCV002060665	benign	Noonan syndrome and Noonan-related syndrome	2021-06-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002429417	SCV002727335	benign	Cardiovascular phenotype	2020-01-15	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Genome-Nilou Lab	RCV001084628	SCV002763052	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001084628	SCV003799763	benign	Noonan syndrome 9	2023-10-13	criteria provided, single submitter	clinical testing