ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2014C>A (p.Leu672Ile) (rs34139502)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000513866 SCV000610577 likely benign not provided 2017-06-20 criteria provided, single submitter clinical testing
Invitae RCV001081985 SCV000656011 benign Noonan syndrome 9 2020-12-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000513866 SCV000698738 benign not provided 2017-04-12 criteria provided, single submitter clinical testing Variant summary: The SOS2 c.2014C>A (p.Leu672Ile) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. The variant lies within the Ras guanine nucleotide exchange factor domain and Ras-like guanine nucleotide exchange factor domain, N-terminal (InterPro). 4/5 in silico tools predict a benign outcome for this variant. This variant was found in the large control database ExAC at a frequency of 0.0019927 (208/104380 control chromosomes [3 homozygotes] in all populations), but was primarily observed in the African subpopulation at a frequency of 0.020296 (189/9312 controls chromosomes [3 homozygotes]). This frequency is about 8118 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), which provides strong evidence that this is likely a benign polymorphism found primarily in populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx RCV000612567 SCV000715216 benign not specified 2017-06-15 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001081985 SCV001477732 likely benign Noonan syndrome 9 2020-05-27 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.