Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000364483 | SCV000329685 | pathogenic | not provided | 2015-12-23 | criteria provided, single submitter | clinical testing | The c.3701delT variant in the GRIN2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.3701delT variant causes a frameshift starting with codon Phenylalanine 1234, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 51 of the new reading frame, denoted p.Phe1234SerfsX51. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 231 amino acids of the protein are replaced by 50 incorrect amino acids. The c.3701delT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.3701delT as a pathogenic variant. |
Genetic Services Laboratory, |
RCV000364483 | SCV003839566 | likely pathogenic | not provided | 2022-07-18 | no assertion criteria provided | clinical testing | DNA sequence analysis of the GRIN2A gene demonstrated a single base pair deletion in exon 14, c.3701del. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 50 amino acids downstream of the change, p.Phe1234Serfs*51. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated GRIN2A protein with potentially abnormal function. While this deletion has not previously been described in the literature, other truncating variants in the GRIN2A gene have been described in several individuals with GRIN2A-related disorders (PMID: 30544257). The c.3701del sequence change has not been described in population databases such as ExAC and gnomAD. This sequence change is likely related to this individual's phenotype, however functional studies have not been performed to prove this conclusively. |