Submissions for variant NM_006939.4(SOS2):c.2350C>T (p.Arg784Cys)

gnomAD frequency: 0.00002  dbSNP: rs760520078

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002220629	SCV002363397	likely benign	Noonan syndrome 9	2024-11-24	criteria provided, single submitter	clinical testing
Clinical Genomics Laboratory, Stanford Medicine	RCV002220629	SCV004804531	uncertain significance	Noonan syndrome 9	2021-06-05	criteria provided, single submitter	clinical testing	• The p.Arg784Cys variant in the SOS2 gene has not been previously reported in association with disease. • This variant has been identified in 11/10,362 Ashkenazi Jewish chromosomes (12/282,574 chromosomes overall) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, it has not been observed at a frequency high enough to rule out pathogenicity. • The arginine at amino acid residue 784 is highly conserved and computational tools predict that the p.Arg784Cys variant is deleterious; however, the accuracy of in silico algorithms is limited. • These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Arg784Cys variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PP3]