ClinVar

Description

The c.262_264delGAG variant has been published as a pathogenic variant in association with transcobalamin II receptor defect in a patient with an abnormal newborn screening result for methylmalonic aciduria as well as in an infant with bilateral central retinal artery occlusions and hyperhomocysteinemia (Quadros et al., 2010; Karth et al., 2012). It has not been reported as a benign variant to our knowledge. However, the 1000 Genomes Project reports c.262_264delGAG was observed in 1.4% of alleles from Asian individuals and in 3.3% of alleles from individuals from Great Britain indicating that c.262_264delGAG may be a rare (benign) variant in these populations. The deletion of three nucleotides results in the loss of a single Glutamic Acid residue at amino acid position 88, denoted p.Glu88del. The loss of this amino acid has been shown to affect the function of the CD320 protein in vitro (Quadros et al., 2010). In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.