Submissions for variant NM_006939.4(SOS2):c.3813G>A (p.Pro1271=)

dbSNP: rs2227276

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000589171	SCV000525683	benign	not provided	2016-09-28	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589171	SCV000698745	benign	not provided	2017-04-11	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.3813G>A (p.Pro1271Pro) 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 introduce an SF2/ASF ESE site at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC at a frequency of 0.1980044 (24031/121366 control chromosomes [2718 homozygotes]), which is approximately 79202 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), strong evidence that this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001195556	SCV001365947	benign	not specified	2018-12-27	criteria provided, single submitter	clinical testing	p.Pro1271Pro in exon 23 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 44.43% (3835/8632) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs2227276).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001518639	SCV001727373	benign	Noonan syndrome 9	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002356567	SCV002620214	benign	Cardiovascular phenotype	2019-01-21	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	RCV001518639	SCV002762971	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589171	SCV005295841	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV001195556	SCV001922959	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001195556	SCV001957279	benign	not specified		no assertion criteria provided	clinical testing