ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.3952C>T (p.Pro1318Ser) (rs140995728)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000555942 SCV000656031 likely benign Noonan syndrome 9 2020-11-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001175493 SCV001339086 likely benign not specified 2020-03-23 criteria provided, single submitter clinical testing Variant summary: SOS2 c.3952C>T (p.Pro1318Ser) results in a non-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 0.0005 in 251440 control chromosomes, predominantly at a frequency of 0.00095 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 380 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 a benign polymorphism found primarily in populations of Non-Finnish European origin. c.3952C>T has been reported in the literature in individuals affected with Noonan Syndrome and Related Conditions, without strong evidence for causality (Cordeddu_2015). This report does not provide unequivocal conclusions about association of the variant with Noonan Syndrome and Related Conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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