ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.1448G>A (p.Ser483Asn) (rs17122201)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000590481 SCV000530491 benign not provided 2016-11-28 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001084971 SCV000656009 benign Noonan syndrome 9 2020-12-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590481 SCV000698737 benign not provided 2017-04-12 criteria provided, single submitter clinical testing Variant summary: The SOS2 c.1448G>A (p.Ser483Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution. The variant lies within the Pleckstrin homology domain (InterPro) and 4/4 in silico tools predict a benign outcome for this variant. This variant was found in the large control database ExAC at a frequency of 0.0084862 in all populations (1030/121374 control chromosomes [39 homozygotes]), but was observed most commonly in the African subpopulation at a frequency of 0.087794 (912/10388 [38 homozygotes]). This frequency is about 35118 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), providing strong evidence that this is likely a benign polymorphism found primarily in the populations of African origin. One publication has reported the variant in 6 individuals diagnosed with RASopathies or Noonan syndrome. However, co-segregation data was not provided and the authors classified the variant as a polymorphism (Cordeddu_HM_2015). In addition, one clinical diagnostic laboratories classified this variant as benign. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001084971 SCV001473585 benign Noonan syndrome 9 2019-11-02 criteria provided, single submitter clinical testing

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