Submissions for variant NM_006939.4(SOS2):c.816T>C (p.Ser272=)

gnomAD frequency: 0.02130  dbSNP: rs35396088

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000532596	SCV000656038	benign	Noonan syndrome 9	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588291	SCV000698750	benign	not provided	2017-04-12	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.816T>C (p.Ser272Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2546/121094 control chromosomes at a frequency of 0.021025, which is approximately 8410 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV000600366	SCV000714248	benign	not specified	2017-03-01	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000600366	SCV001365949	benign	not specified	2018-12-27	criteria provided, single submitter	clinical testing	p.Ser272Ser in exon 6 of SOS2: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 8.61% (568/6600) of Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs35396088).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813503	SCV002060685	benign	Noonan syndrome and Noonan-related syndrome	2021-06-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002431706	SCV002680436	benign	Cardiovascular phenotype	2019-05-17	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Genome-Nilou Lab	RCV000532596	SCV002763109	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588291	SCV005289540	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000600366	SCV001926154	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000600366	SCV001959151	benign	not specified		no assertion criteria provided	clinical testing