Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192666 | SCV001360925 | likely pathogenic | Intellectual disability, autosomal dominant 6 | 2019-03-05 | criteria provided, single submitter | clinical testing | Variant summary: The variant, GRIN2B c.1675T>C (p.Trp559Arg) results in a non-conservative amino acid change located in the Ionotropic glutamate receptor domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 277128 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1675T>C in individuals affected with Mental retardation, autosomal dominant 6 and no experimental evidence demonstrating its impact on protein function have been reported. However, our internal whole exome testing showed that this variant was found in a patient with mental retardation as a de novo variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV001214413 | SCV001386095 | pathogenic | Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 | 2022-08-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GRIN2B protein function. ClinVar contains an entry for this variant (Variation ID: 928560). This missense change has been observed in individual(s) with clinical features of GRIN2B-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 559 of the GRIN2B protein (p.Trp559Arg). |
| 3billion, |
RCV001192666 | SCV002573104 | likely pathogenic | Intellectual disability, autosomal dominant 6 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.89; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported as likely pathogenic (ClinVar ID: VCV000928560). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |