Submissions for variant NM_006939.4(SOS2):c.970-19A>G

gnomAD frequency: 0.00004  dbSNP: rs369274700

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000611398	SCV000714641	benign	not specified	2017-03-22	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	RCV000611398	SCV001372297	benign	not specified	2020-06-10	criteria provided, single submitter	clinical testing	Variant summary: SOS2 c.970-19A>G alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.00053 in 242098 control chromosomes, predominantly at a frequency of 0.0036 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1440 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.970-19A>G in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002062816	SCV002462433	benign	Noonan syndrome 9	2023-12-21	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002062816	SCV002763103	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing