ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.3758G>C (p.Ser1253Thr)

gnomAD frequency: 0.00002  dbSNP: rs762593451
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001236571 SCV001409300 likely benign Noonan syndrome 9 2022-09-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587089 SCV005076113 likely benign not specified 2024-04-16 criteria provided, single submitter clinical testing Variant summary: SOS2 c.3758G>C (p.Ser1253Thr) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 1614038 control chromosomes, predominantly at a frequency of 5.9e-05 within the Non-Finnish European subpopulation in the gnomAD database (v4.0.0). The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 24 fold of 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 a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.3758G>C in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 962676). Based on the evidence outlined above, the variant was classified as likely benign.

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