GRIN2D is a highly conserved gene that is according to gnomAD (v2.1.1, https://gnomad.broadinstitute.org/) depleted for both missense (Z = 4.85) and null variants (pLI = 1.00; LOEUF = 0.17) and pathogenic heterozygous missense variants are generally of de novo origin. As GRIN2D-related disorder is currently still the least frequently observed type of GRIN disorders, a valid statement on clustering of missense variants is not yet possible. GRIN2D null variants (other than larger contiguous gene deletions) have thus far not been observed and their association to GRIN2D-related neurodevelopmental disorder currently remain unclear as well.
GRIN2D-related neurodevelopmental disorders are inherited in an autosomal dominant manner. The diagnosis of a GRIN2D-related neurodevelopmental disorder is established in a proband by identification of either a heterozygous pathogenic variant of GRIN2D on molecular genetic testing.
GRIN2D