Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001386843 | SCV001587215 | pathogenic | Neonatal-onset encephalopathy with rigidity and seizures | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu152Ilefs*70) in the BRAT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRAT1 are known to be pathogenic (PMID: 22279524, 25500575). This variant is present in population databases (rs727505362, gnomAD 0.05%). This premature translational stop signal has been observed in individual(s) with clinical features of neonatal-lethal rigidity and multifocal seizure syndrome (PMID: 23035047). ClinVar contains an entry for this variant (Variation ID: 1073760). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002286844 | SCV002577305 | likely pathogenic | not provided | 2022-03-29 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25500575, 22279524, 25319849, 26947546, 30346566, 27282648, 27282546, 25937001, 23035047, Fernandez-Jaen2016[Review]) |
Illumina Laboratory Services, |
RCV003314690 | SCV004014749 | pathogenic | Neurodevelopmental disorder with cerebellar atrophy and with or without seizures | 2023-04-24 | criteria provided, single submitter | clinical testing | The BRAT1 c.453_454insATCTTCTC (p.Leu152IlefsTer70) frameshift variant results in the loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in a homozygous state in a female with lethal neonatal rigidity and multifocal seizure syndrome (PMID: 23035047; 25937001). The highest frequency of this allele in the Genome Aggregation Database is 0.000519 in the Latino/Admixed American population (version 2.1.1). Based on the available evidence the c.453_454insATCTTCTC (p.Leu152IlefsTer70) variant is classified as pathogenic for neurodevelopmental disorder with cerebellar atrophy and with or without seizures. |
Prevention |
RCV003416308 | SCV004117467 | likely pathogenic | BRAT1-related condition | 2022-09-20 | criteria provided, single submitter | clinical testing | The BRAT1 c.453_454insATCTTCTC variant is predicted to result in a frameshift and premature protein termination (p.Leu152Ilefs*70). This variant was reported in homozygous state in an individual with neonatal epilepsy (Saunders et al. 2012. PubMed ID: 23035047). This variant is reported in 0.052% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-2583573-G-GGAGAAGAT). Frameshift variants in BRAT1 are expected to be pathogenic. This variant is interpreted as likely pathogenic. |