Submissions for variant NM_006939.4(SOS2):c.3088A>G (p.Thr1030Ala)

gnomAD frequency: 0.00010  dbSNP: rs550680554

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000559916	SCV000656023	likely benign	Noonan syndrome 9	2023-11-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001251388	SCV001426971	likely benign	not specified	2020-07-13	criteria provided, single submitter	clinical testing	Variant summary: SOS2 c.3088A>G (p.Thr1030Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 240566 control chromosomes. The observed variant frequency is approximately 75 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS2 causing Noonan Syndrome And Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3088A>G in individuals affected with Noonan Syndrome And Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics	RCV002325091	SCV002608742	likely benign	Cardiovascular phenotype	2022-06-22	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	RCV000559916	SCV002763008	likely benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003392402	SCV004134077	benign	not provided	2022-08-01	criteria provided, single submitter	clinical testing	SOS2: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV003392402	SCV005211995	likely benign	not provided		criteria provided, single submitter	not provided
Service de Génétique Moléculaire, Hôpital Robert Debré	RCV001261127	SCV001438534	likely benign	Noonan syndrome		no assertion criteria provided	clinical testing