ClinVar

Description

Variant summary: The SOS2 c.2014C>A (p.Leu672Ile) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. The variant lies within the Ras guanine nucleotide exchange factor domain and Ras-like guanine nucleotide exchange factor domain, N-terminal (InterPro). 4/5 in silico tools predict a benign outcome for this variant. This variant was found in the large control database ExAC at a frequency of 0.0019927 (208/104380 control chromosomes [3 homozygotes] in all populations), but was primarily observed in the African subpopulation at a frequency of 0.020296 (189/9312 controls chromosomes [3 homozygotes]). This frequency is about 8118 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), which provides strong evidence that this is likely a benign polymorphism found primarily in populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.