Submissions for variant NM_006939.4(SOS2):c.622G>A (p.Ala208Thr)

dbSNP: rs61755579

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000586888	SCV000525860	benign	not provided	2016-10-25	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	RCV000554272	SCV000656037	benign	Noonan syndrome 9	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586888	SCV000698749	benign	not provided	2017-04-12	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.622G>A (p.Ala208Thr) 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). This variant was found in 2245/121196 control chromosomes at a frequency of 0.0185237, which is approximately 7409 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000554272	SCV001159482	benign	Noonan syndrome 9	2023-11-09	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813479	SCV002060683	benign	Noonan syndrome and Noonan-related syndrome	2021-07-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365514	SCV002658238	benign	Cardiovascular phenotype	2019-03-12	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	RCV000554272	SCV002763124	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586888	SCV004134091	benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	SOS2: BS1, BS2