Submissions for variant NM_006939.4(SOS2):c.2232C>T (p.Asn744=)

gnomAD frequency: 0.60005  dbSNP: rs2229869

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000587035	SCV000525680	benign	not provided	2016-09-29	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	RCV000587035	SCV000698735	benign	not provided	2017-04-12	criteria provided, single submitter	clinical testing	Variant summary: The SOS2 c.2232C>T (p.Asn744Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of two ESE sites. However, these predictions have not been confirmed by functional studies. This variant was found in 75437/121388 control chromosomes from ExAC (23983 homozygotes) at a frequency of 0.6214535, thus allele T is the major allele at this position. One clinical diagnostic laboratory has classified this variant as benign. Therefore, this variant is classified as Benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV001195557	SCV001365948	benign	not specified	2018-12-27	criteria provided, single submitter	clinical testing	p.Asn744Asn in exon 14 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 68.67% (45825/66736) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs2229869).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001515861	SCV001724028	benign	Noonan syndrome 9	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001515861	SCV002057533	benign	Noonan syndrome 9	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002429401	SCV002726760	benign	Cardiovascular phenotype	2018-12-11	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.
Breakthrough Genomics, Breakthrough Genomics	RCV000587035	SCV005289318	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV001195557	SCV001924702	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001195557	SCV001955559	benign	not specified		no assertion criteria provided	clinical testing