Submissions for variant NM_006939.4(SOS2):c.2786-18dup

dbSNP: rs201957103

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001704835	SCV000731087	benign	not provided	2018-06-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000604982	SCV001361618	benign	not specified	2019-08-19	criteria provided, single submitter	clinical testing	Variant summary: SOS2 c.2786-6dupT 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. The variant allele was found at a frequency of 0.21 in 55180 control chromosomes in the gnomAD database, including 621 homozygotes. The observed variant frequency is approximately 80000 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.2786-6dupT in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001518640	SCV001727374	benign	Noonan syndrome 9	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001518640	SCV002763025	benign	Noonan syndrome 9		criteria provided, single submitter	clinical testing