Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001037132.4(NRCAM):c.3587G>A(p.Gly1196Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
NRCAM (HGNC:7994): (neuronal cell adhesion molecule) Cell adhesion molecules (CAMs) are members of the immunoglobulin superfamily. This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III domains. This ankyrin-binding protein is involved in neuron-neuron adhesion and promotes directional signaling during axonal cone growth. This gene is also expressed in non-neural tissues and may play a general role in cell-cell communication via signaling from its intracellular domain to the actin cytoskeleton during directional cell migration. Allelic variants of this gene have been associated with autism and addiction vulnerability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.3587G>A (p.G1196D) alteration is located in exon 28 (coding exon 28) of the NRCAM gene. This alteration results from a G to A substitution at nucleotide position 3587, causing the glycine (G) at amino acid position 1196 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -