ClinVar Genomic variation as it relates to human health
NM_152743.4(BRAT1):c.638dup (p.Val214fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_152743.4(BRAT1):c.638dup (p.Val214fs)
Variation ID: 31199 Accession: VCV000031199.59
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 7p22.3 7: 2543754-2543755 (GRCh38) [ NCBI UCSC ] 7: 2583388-2583389 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 19, 2017 Apr 15, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152743.4:c.638dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689956.2:p.Val214fs frameshift NM_001350626.1:c.638dup NM_001350626.2:c.638dup NP_001337555.1:p.Val214fs frameshift NM_001350626.2:c.638dupA NM_001350627.2:c.113dup NP_001337556.1:p.Val39fs frameshift NM_152743.3:c.638dupA NR_146879.2:n.697dup non-coding transcript variant NC_000007.14:g.2543756dup NC_000007.13:g.2583390dup NG_032167.1:g.17004dup - Protein change
- V214fs, V39fs
- Other names
- -
- Canonical SPDI
- NC_000007.14:2543754:TT:TTT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BRAT1 | - | - |
GRCh38 GRCh37 |
1191 | 1248 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2024 | RCV000024198.21 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 25, 2017 | RCV000210714.6 | |
Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000268435.37 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2023 | RCV000677127.7 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV003335054.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Dec 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000858549.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
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Pathogenic
(Jul 10, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Neonatal-onset encephalopathy with rigidity and seizures
Affected status: yes
Allele origin:
maternal
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000966181.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
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Pathogenic
(Apr 20, 2018)
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criteria provided, single submitter
Method: clinical testing
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RIGIDITY AND MULTIFOCAL SEIZURE SYNDROME, LETHAL NEONATAL
Affected status: yes
Allele origin:
germline
|
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV000996134.1
First in ClinVar: Oct 19, 2019 Last updated: Oct 19, 2019 |
Comment:
This frameshifting variant is predicted to result in a premature stop codon and is therefore considered a loss-of-function mutation. This variant has been detected as … (more)
This frameshifting variant is predicted to result in a premature stop codon and is therefore considered a loss-of-function mutation. This variant has been detected as a homozygous change in individuals with lethal neonatal rigidity and seizure syndrome (PMID: 22279524). It has also been reported in the compound heterozygous state in individuals with milder phenotypes (PMID: 27282648, 27282546). This variant is present as a heterozygous change in the gnomAD population database at a frequency of 0.024%. Based on the available evidence, the c.638dupA (p.Val214GlyfsTer189) variant is classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Sep 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Neonatal-onset encephalopathy with rigidity and seizures
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002011887.1
First in ClinVar: Nov 11, 2021 Last updated: Nov 11, 2021 |
Comment:
The c.638dup;p.(Val214Glyfs*189) is a null frameshift variant in the BRAT1 gene with an insertion of 1 base pair - PVS1; well-established in vitro or in … (more)
The c.638dup;p.(Val214Glyfs*189) is a null frameshift variant in the BRAT1 gene with an insertion of 1 base pair - PVS1; well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 22279524) - PS3; this variant has been reported as homozygous or compound heterozygous in several individuals with lethal neonatal rigidity and seizure syndrome (PMID: 27282648; 27282546; 22279524; 26535877; 26535877; 26947546 and GeneOne, DASA), and ClinVar contains an entry for this variant (Clinvar ID: 31199) - PS4; this variant is present in population databases (rs730880324, gnomAD frequency 0.02%; ABraOM frequency 0.04% - http://abraom.ib.usp.br/); variant detected in trans with a pathogenic variant (PMID: 27282648; 27282546; 22279524; 26535877; 26535877; 26947546) - PM3_strong; this variant has been observed to segregate in families (PMID: 27282648; 27282546; 26535877; 26947546) - PP1_strong. For these reasons, this variant was classified as pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
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Pathogenic
(Dec 13, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002064447.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Pathogenic
(Sep 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with cerebellar atrophy and with or without seizures
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin
Additional submitter:
CUBI - Core Unit Bioinformatics, Berlin Institute of Health
Accession: SCV002574864.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
Clinical Features:
Seizure (present) , Encephalopathy (present) , Respiratory insufficiency (present)
Sex: female
Tissue: Blood
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Pathogenic
(Apr 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Neonatal-onset encephalopathy with rigidity and seizures
Affected status: yes
Allele origin:
germline
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Centogene AG - the Rare Disease Company
Accession: SCV002598521.1
First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022 |
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Pathogenic
(Jan 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000329115.8
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate aggregation of mutant BRAT1 protein in the cytoplasm suggesting protein destabilization (Puffenberger et al., 2012); Frameshift variant predicted to result in … (more)
Published functional studies demonstrate aggregation of mutant BRAT1 protein in the cytoplasm suggesting protein destabilization (Puffenberger et al., 2012); 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: 25356970, 22279524, 26494257, 25319849, 27282546, 26535877, 26947546, 29997391, 30552426, 31028937, 27282648, 31589614, 31980526, 34426522, 25500575) (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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BRAT1-Related Disorders
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV004046010.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Comment:
This frameshifting variant in exon 5 of 14 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function … (more)
This frameshifting variant in exon 5 of 14 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as a homozygous change in multiple individuals with Lethal Neonatal Rigidity & Seizure Syndrome (PMID: 22279524, 26535877, 26947546, 27282648, 27282546). It has also been reported in the compound heterozygous state in individuals with milder phenotypes (PMID: 27282648, 27282546). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.024% (66/279484) and thus is presumed to be rare. Based on the available evidence, the c.638dup (p.Val214GlyfsTer189) variant is classified as Pathogenic. (less)
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Pathogenic
(Apr 19, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022747.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Neonatal-onset encephalopathy with rigidity and seizures
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000652273.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val214Glyfs*189) in the BRAT1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Val214Glyfs*189) 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 (rs730880324, gnomAD 0.05%). This premature translational stop signal has been observed in individuals with lethal neonatal rigidity and seizure syndrome and/or progressive encephalopathy, early-onset epileptic encephalopathy, ataxia, and developmental delay (PMID: 22279524, 26535877, 26947546, 27282546, 27282648). This variant is also known as c.638_639insA. ClinVar contains an entry for this variant (Variation ID: 31199). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Oct 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with cerebellar atrophy and with or without seizures
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV001480278.1 First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Clinical Features:
Intellectual disability (present) , Seizure (present) , Autism (present) , Attention deficit hyperactivity disorder (present)
Secondary finding: no
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Pathogenic
(Jan 25, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: yes
Allele origin:
germline
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Ambry Genetics
Accession: SCV000262862.6
First in ClinVar: Apr 09, 2016 Last updated: Jan 07, 2023 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Cerebellar atrophy (present) , Intellectual disability (present) , Delayed speech and language development (present) , Inappropriate behavior (present) , Cerebellar ataxia (present) , Dysmetria (present) … (more)
Cerebellar atrophy (present) , Intellectual disability (present) , Delayed speech and language development (present) , Inappropriate behavior (present) , Cerebellar ataxia (present) , Dysmetria (present) , Apraxia (present) , Abnormal facial shape (present) , Muscular hypotonia (present) , Microcephaly (present) (less)
Sex: female
Ethnicity/Population group: Caucasian
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Seizures (present) , Generalized myoclonic seizures (present) , Aspiration (present) , Dysphagia (present) , Gastrostomy tube feeding in infancy (present) , Respiratory failure (present) , … (more)
Seizures (present) , Generalized myoclonic seizures (present) , Aspiration (present) , Dysphagia (present) , Gastrostomy tube feeding in infancy (present) , Respiratory failure (present) , Hypoglycemia (present) , Small anterior fontanelle (present) , Hypotelorism (present) , Midface retrusion (present) , High, narrow palate (present) , Single transverse palmar crease (present) , Posteriorly rotated ears (present) , Hypoplasia of the antihelix (present) , Clubfoot (present) , Overlapping toe (present) , Short neck (present) , Low posterior hairline (present) (less)
Sex: female
Ethnicity/Population group: Caucasian/Norwegian/German
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Pathogenic
(Jun 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder with cerebellar atrophy and with or without seizures
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004020394.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
Variant summary: C7orf27 (BRAT1) c.638dupA (p.Val214GlyfsX189) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the … (more)
Variant summary: C7orf27 (BRAT1) c.638dupA (p.Val214GlyfsX189) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00024 in 279484 control chromosomes (gnomAD). c.638dupA has been reported in the literature as a biallelic genotype in individuals affected with lethal neonatal rigidity and seizure syndrome, neurodevelopmental disorder with cerebellar atrophy, and in individuals with nonprogressive congenital ataxia and shrunken cerebellum (e.g. Puffenberger_2012, Nuovo_2022). These data indicate that the variant is very likely to be associated with disease. Additionally, overexpression of the variant protein in vitro resulted in abolished nuclear localization and demonstrated protein instability (e.g. Puffenberger_2012). The following publications have been ascertained in the context of this evaluation (PMID: 34747546, 22279524). Fourteen submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic (n=13)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247246.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Comment:
BRAT1: PP1:Strong, PVS1:Strong, PS3:Moderate
Number of individuals with the variant: 4
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Pathogenic
(Jan 01, 2012)
|
no assertion criteria provided
Method: literature only
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RIGIDITY AND MULTIFOCAL SEIZURE SYNDROME, LETHAL NEONATAL
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000045489.4
First in ClinVar: Apr 04, 2013 Last updated: Aug 05, 2018 |
Comment on evidence:
By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome (RMFSL; 614498), Puffenberger et … (more)
By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome (RMFSL; 614498), Puffenberger et al. (2012) identified a homozygous 1-bp insertion (638_639insA) in the BRAT1 gene, resulting in a frameshift and premature termination. Two unrelated Old Order Amish infants from different demes in Wisconsin and Kentucky with a similar phenotype were found to carry the same homozygous mutation. Two heterozygous carriers of this mutation were found among 201 Old Order Amish control samples, yielding a population-specific allele frequency of 0.50%. The mutation abolished the nuclear localization signal, and rendered the protein unstable when expressed in human cells as shown by Western blot analysis. Puffenberger et al. (2012) suggested that the mutation abolishes the interaction of BRAT1 with BRCA1. In 3 sibs, born of consanguineous Moroccan parents, with RMFSL, van de Pol et al. (2015) identified a c.638dupA mutation in the BRAT1 gene, predicted to result in a frameshift and premature termination (Val214GlyfsTer189). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, was confirmed by Sanger sequencing and segregated with the disorder in the family. The mutation was filtered against the dbSNP (build 137), 1000 Genomes Project, and Exome Sequencing Project databases, and was found at a low frequency (0.06%) in control databases. Functional studies of the variant and studies of patient cells were not performed. The mutation was the same as that reported by Puffenberger et al. (2012) in Amish patients, suggesting that it is not a founder mutation, but rather arose independently. Van de Pol et al. (2015) recommended that the BRAT1 gene be included in gene panels for epileptic encephalopathy. In 2 sisters (patients 1 and 2) with neurodevelopmental disorder with cerebellar atrophy, with or without seizures (NEDCAS; 618056), Srivastava et al. (2016) identified compound heterozygous mutations in the BRAT1 gene: the c.638dupA mutation and a splice site mutation (614506.0008). An unrelated patient (patient 3) with NEDCAS was found to have the c.638dupA mutation on 1 allele and a missense mutation (L140P; 614506.0009) in the BRAT1 gene on the other allele. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The c.638dupA gene was found at low frequencies in the ExAC database (0.00051) and in the Exome Variant Server (0.00085). The splice site mutation and L140P were not observed in either database. Functional studies of the variants and studies of patient cells were not performed. (less)
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Pathogenic
(Jan 01, 2012)
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no assertion criteria provided
Method: literature only
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NEURODEVELOPMENTAL DISORDER WITH CEREBELLAR ATROPHY AND WITH OR WITHOUT SEIZURES
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000803197.1
First in ClinVar: Aug 06, 2018 Last updated: Aug 06, 2018 |
Comment on evidence:
By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome (RMFSL; 614498), Puffenberger et … (more)
By homozygosity mapping followed by exome sequencing of 2 Amish patients from Pennsylvania with lethal neonatal rigidity and multifocal seizure syndrome (RMFSL; 614498), Puffenberger et al. (2012) identified a homozygous 1-bp insertion (638_639insA) in the BRAT1 gene, resulting in a frameshift and premature termination. Two unrelated Old Order Amish infants from different demes in Wisconsin and Kentucky with a similar phenotype were found to carry the same homozygous mutation. Two heterozygous carriers of this mutation were found among 201 Old Order Amish control samples, yielding a population-specific allele frequency of 0.50%. The mutation abolished the nuclear localization signal, and rendered the protein unstable when expressed in human cells as shown by Western blot analysis. Puffenberger et al. (2012) suggested that the mutation abolishes the interaction of BRAT1 with BRCA1. In 3 sibs, born of consanguineous Moroccan parents, with RMFSL, van de Pol et al. (2015) identified a c.638dupA mutation in the BRAT1 gene, predicted to result in a frameshift and premature termination (Val214GlyfsTer189). The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, was confirmed by Sanger sequencing and segregated with the disorder in the family. The mutation was filtered against the dbSNP (build 137), 1000 Genomes Project, and Exome Sequencing Project databases, and was found at a low frequency (0.06%) in control databases. Functional studies of the variant and studies of patient cells were not performed. The mutation was the same as that reported by Puffenberger et al. (2012) in Amish patients, suggesting that it is not a founder mutation, but rather arose independently. Van de Pol et al. (2015) recommended that the BRAT1 gene be included in gene panels for epileptic encephalopathy. In 2 sisters (patients 1 and 2) with neurodevelopmental disorder with cerebellar atrophy, with or without seizures (NEDCAS; 618056), Srivastava et al. (2016) identified compound heterozygous mutations in the BRAT1 gene: the c.638dupA mutation and a splice site mutation (614506.0008). An unrelated patient (patient 3) with NEDCAS was found to have the c.638dupA mutation on 1 allele and a missense mutation (L140P; 614506.0009) in the BRAT1 gene on the other allele. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The c.638dupA gene was found at low frequencies in the ExAC database (0.00051) and in the Exome Variant Server (0.00085). The splice site mutation and L140P were not observed in either database. Functional studies of the variants and studies of patient cells were not performed. (less)
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Pathogenic
(Jan 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Rigidity and multifocal seizure syndrome, lethal neonatal
Affected status: yes
Allele origin:
biparental
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Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV001427430.1
First in ClinVar: Aug 13, 2020 Last updated: Aug 13, 2020 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807205.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001744763.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001970503.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001979341.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
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not provided
(-)
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no classification provided
Method: phenotyping only
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NEURODEVELOPMENTAL DISORDER WITH CEREBELLAR ATROPHY AND WITH OR WITHOUT SEIZURES
Affected status: unknown
Allele origin:
maternal
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GenomeConnect, ClinGen
Accession: SCV001423323.1
First in ClinVar: Jul 19, 2020 Last updated: Jul 19, 2020 |
Comment:
Variant interpretted as Pathogenic and reported on 05-31-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpretted as Pathogenic and reported on 05-31-2018 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Prenatal maternal abnormality (present) , Short stature (present) , Growth hormone deficiency (present) , Cerebral palsy (present) , Cognitive impairment (present) , Abnormality of coordination … (more)
Prenatal maternal abnormality (present) , Short stature (present) , Growth hormone deficiency (present) , Cerebral palsy (present) , Cognitive impairment (present) , Abnormality of coordination (present) , EEG abnormality (present) , Generalized hypotonia (present) , Memory impairment (present) , Seizures (present) , Autistic behavior (present) , Stereotypy (present) , Short attention span (present) , Abnormality of limb bone morphology (present) , Abnormality of the curvature of the vertebral column (present) , Joint hypermobility (present) , Abnormality of the foot (present) , Abnormality of muscle physiology (present) , Abnormality of the musculature of the limbs (present) , Misalignment of teeth (present) (less)
Indication for testing: Diagnostic
Age: 10-19 years
Sex: female
Method: Sanger Sequencing
Testing laboratory: GeneDx
Date variant was reported to submitter: 2018-05-31
Testing laboratory interpretation: Pathogenic
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Clinical variability at the mild end of BRAT1-related spectrum: Evidence from two families with genotype-phenotype discordance. | Nuovo S | Human mutation | 2022 | PMID: 34747546 |
BRAT1 mutations are associated with infantile epileptic encephalopathy, mitochondrial dysfunction, and survival into childhood. | Horn D | American journal of medical genetics. Part A | 2016 | PMID: 27282648 |
BRAT1 mutations present with a spectrum of clinical severity. | Srivastava S | American journal of medical genetics. Part A | 2016 | PMID: 27282546 |
Mutations in BRAT1 cause autosomal recessive progressive encephalopathy: Report of a Spanish patient. | Fernández-Jaén A | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society | 2016 | PMID: 26947546 |
Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes. | van de Pol LA | Neuropediatrics | 2015 | PMID: 26535877 |
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Lethal neonatal rigidity and multifocal seizure syndrome--report of another family with a BRAT1 mutation. | Straussberg R | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society | 2015 | PMID: 25500575 |
Genetic mapping and exome sequencing identify variants associated with five novel diseases. | Puffenberger EG | PloS one | 2012 | PMID: 22279524 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRAT1 | - | - | - | - |
Text-mined citations for rs730880324 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.