Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001251318 | SCV001426868 | benign | not specified | 2020-07-20 | criteria provided, single submitter | clinical testing | Variant summary: SOS2 c.1609G>T (p.Ala537Ser) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.8e-05 in 251012 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 27-fold the estimated maximal expected allele frequency for a pathogenic variant in SOS2 causing Noonan Syndrome phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1609G>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No other 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. |
Invitae | RCV001879819 | SCV002198081 | likely benign | Noonan syndrome 9 | 2023-09-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002393667 | SCV002703112 | uncertain significance | Cardiovascular phenotype | 2022-09-02 | criteria provided, single submitter | clinical testing | The p.A537S variant (also known as c.1609G>T), located in coding exon 10 of the SOS2 gene, results from a G to T substitution at nucleotide position 1609. The alanine at codon 537 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |