Submissions for variant NM_001134407.3(GRIN2A):c.82_84del (p.Glu28del)

dbSNP: rs767188122

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484425	SCV000573409	uncertain significance	not provided	2017-02-17	criteria provided, single submitter	clinical testing	The c.82_84delGAG variant in the GRIN2A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.82_84delGAG variant results in the in-frame deletion of three base pairs, which is predicted to cause loss of the Glutamic Acid residue at position 28 in the protein, denoted p.Glu28del. The deleted residue is conserved through mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The c.82_84delGAG variant is not observed with any significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.82_84delGAG as a variant of uncertain significance.
Invitae	RCV001865480	SCV002166144	uncertain significance	Landau-Kleffner syndrome	2023-09-27	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 423684). This variant has been observed in at least one individual who was not affected with GRIN2A-related conditions (Invitae). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. This variant is present in population databases (rs767188122, gnomAD 0.002%). This variant, c.82_84del, results in the deletion of 1 amino acid(s) of the GRIN2A protein (p.Glu28del), but otherwise preserves the integrity of the reading frame.