Submissions for variant NM_006939.4(SOS2):c.572C>G (p.Pro191Arg)

gnomAD frequency: 0.00421  dbSNP: rs72681869

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000513780	SCV000609920	benign	not provided	2017-02-24	criteria provided, single submitter	clinical testing
Invitae	RCV000989216	SCV000656033	benign	Noonan syndrome 9	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000513780	SCV000698747	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.572C>G (p.Pro191Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). The variant of interest has been found in a large, broad control population, ExAC in 554/120618 control chromosomes (1 homozygote) at a frequency of 0.004593, which is approximately 1837 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 clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV000613515	SCV000714912	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.
Mendelics	RCV000989216	SCV001139445	likely benign	Noonan syndrome 9	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000989216	SCV001477756	benign	Noonan syndrome 9	2023-11-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813488	SCV002060681	benign	Noonan syndrome and Noonan-related syndrome	2021-06-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513780	SCV002545175	benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	SOS2: BS1, BS2
Ambry Genetics	RCV002350134	SCV002650653	likely benign	Cardiovascular phenotype	2019-03-12	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.
Genome-Nilou Lab	RCV000989216	SCV002763128	likely benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000613515	SCV001921483	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000513780	SCV001964359	likely benign	not provided		no assertion criteria provided	clinical testing