ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.2162-10C>T (rs375702667)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538946 SCV000656013 likely benign Noonan syndrome 9 2020-10-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001175095 SCV001338665 benign not specified 2020-04-27 criteria provided, single submitter clinical testing Variant summary: SOS2 c.2162-10C>T 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 0.00057 in 250014 control chromosomes (gnomAD). The observed variant frequency is approximately 229 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.2162-10C>T in individuals affected with Noonan Syndrome And Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been reported (PTPN11 c.844A>G, p.I282V) for this variant in our internal database. One ClinVar submitter (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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