Submissions for variant NM_000834.5(GRIN2B):c.2201C>T (p.Ala734Val)

dbSNP: rs876661064

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000222391	SCV000279434	likely pathogenic	not provided	2015-09-28	criteria provided, single submitter	clinical testing	The A734V variant in the GRIN2B gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The A734V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A734V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The A734V variant is a strong candidate for a pathogenic variant. However, the possibility it may be a rare benign variant cannot be excluded.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001172326	SCV001335351	likely pathogenic	Intellectual disability, autosomal dominant 6	2017-04-04	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).