ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.2673+14T>C (rs183998234)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV001030076 SCV001192864 benign Rasopathy 2019-08-27 reviewed by expert panel curation The c.2673+14T>C intronic variant in SOS1 is classified as benign because it has been identified in 0.34596% (lower bound of the 95% CI of 481/128770) of non-Finnish European chromosomes in gnomAD (BA1; https://gnomad.broadinstitute.org). This variant was observed in 1 individual with Noonan syndrome who also carried a pathogenic variant in SHOC2 sufficient to explain their clinical presentation (BP5; SCV000062214.5). ACMG/AMP Criteria applied: BA1, BP5.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038536 SCV000062214 benign not specified 2012-03-19 criteria provided, single submitter clinical testing c.2673+14T>C in Intron 16 of SOS1: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and has been identified in 0.4% (25/7020) of European American chromosomes from a b road population by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS;).
GeneDx RCV000038536 SCV000171776 benign not specified 2012-05-11 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.
PreventionGenetics,PreventionGenetics RCV000038536 SCV000311192 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001094646 SCV000430425 likely benign Noonan syndrome 4 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000312601 SCV000430426 benign Gingival fibromatosis 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852768 SCV000995487 likely benign Hypertrophic cardiomyopathy 2019-04-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000038536 SCV001157519 benign not specified 2019-02-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000038536 SCV001361398 benign not specified 2019-09-25 criteria provided, single submitter clinical testing Variant summary: SOS1 c.2673+14T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0021 in 250818 control chromosomes, predominantly at a frequency of 0.0037 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 123-folds over the estimated maximal expected allele frequency for a pathogenic variant in SOS1 causing Noonan Syndrome and Related Conditions phenotype (3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.2673+14T>C has been reported in the literature in individuals affected with Noonan Syndrome and Related Conditions (Lepri_2011). However, authors indicate the variant is unrelated to disease. A ClinVar submission (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000157009 SCV000206735 benign Noonan syndrome 2012-05-31 no assertion criteria provided 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.