Submissions for variant NM_006939.4(SOS2):c.2384+5A>G

gnomAD frequency: 0.00002  dbSNP: rs376903120

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000546804	SCV000656016	uncertain significance	Noonan syndrome 9	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change falls in intron 14 of the SOS2 gene. It does not directly change the encoded amino acid sequence of the SOS2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs376903120, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SOS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 475745). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000546804	SCV002780442	uncertain significance	Noonan syndrome 9	2021-11-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003962606	SCV004782220	likely benign	SOS2-related condition	2024-02-01	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).