Submissions for variant NM_006939.4(SOS2):c.2786-6del

dbSNP: rs201957103

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175492	SCV001339085	benign	not specified	2020-03-23	criteria provided, single submitter	clinical testing	Variant summary: SOS2 c.2786-6delT 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. 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 0.23 in 31004 control chromosomes in the gnomAD database, including 9 homozygotes. The observed variant frequency is approximately 92155 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 benign. To our knowledge, no occurrence of c.2786-6delT in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001515860	SCV001724027	benign	Noonan syndrome 9	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001712867	SCV001944916	benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001515860	SCV002763026	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing