Submissions for variant NM_006939.4(SOS2):c.2520A>G (p.Ala840=)

gnomAD frequency: 0.00009  dbSNP: rs775682587

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	RCV000587285	SCV000698741	benign	not provided	2017-04-12	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.2520A>G (p.Ala840Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. These predictions have not been confirmed by functional studies. This variant was found in 105/119170 control chromosomes from ExAC, predominantly observed in the Latino subpopulation at a frequency of 0.009083 (105/11560). This frequency is about 3633 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 Latino origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085249	SCV000774694	benign	Noonan syndrome 9	2025-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002456289	SCV002738663	likely benign	Cardiovascular phenotype	2022-04-29	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	RCV001085249	SCV002763036	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925757	SCV004742856	benign	SOS2-related disorder	2019-09-30	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).