Submissions for variant NM_152743.4(BRAT1):c.393_422del (p.Gln132_Ala141del)

dbSNP: rs1562582216

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000714794	SCV000845527	uncertain significance	Neonatal-onset encephalopathy with rigidity and seizures	2018-08-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000714794	SCV001518357	pathogenic	Neonatal-onset encephalopathy with rigidity and seizures	2023-07-19	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BRAT1 protein in which other variant(s) (p.Leu140Pro) have been determined to be pathogenic (PMID: 27282546). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 587574). This variant has been observed in individual(s) with clinical features of BRAT1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This variant, c.393_422del, results in the deletion of 10 amino acid(s) of the BRAT1 protein (p.Gln132_Ala141del), but otherwise preserves the integrity of the reading frame.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV002282344	SCV002570490	uncertain significance	Neurodevelopmental disorder with cerebellar atrophy and with or without seizures		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003141719	SCV003828542	uncertain significance	not provided	2023-11-13	criteria provided, single submitter	clinical testing
GeneDx	RCV003141719	SCV005081314	likely pathogenic	not provided	2023-11-15	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of 10 amino acids in a non-repeat region; This variant is associated with the following publications: (PMID: 37344571)