NM_152743.4(BRAT1):c.1313_1314del (p.Gln438fs) AND Rigidity and multifocal seizure syndrome, lethal neonatal

Clinical significance:Pathogenic (Last evaluated: Sep 29, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000556965.6

Allele description [Variation Report for NM_152743.4(BRAT1):c.1313_1314del (p.Gln438fs)]

NM_152743.4(BRAT1):c.1313_1314del (p.Gln438fs)

Gene:
BRAT1:BRCA1 associated ATM activator 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
7p22.3
Genomic location:
Preferred name:
NM_152743.4(BRAT1):c.1313_1314del (p.Gln438fs)
HGVS:
  • NC_000007.14:g.2541305_2541306del
  • NG_032167.1:g.19453_19454del
  • NM_001350626.2:c.1313_1314del
  • NM_001350627.2:c.788_789del
  • NM_152743.4:c.1313_1314delMANE SELECT
  • NP_001337555.1:p.Gln438fs
  • NP_001337556.1:p.Gln263fs
  • NP_689956.2:p.Gln438fs
  • NC_000007.13:g.2580939_2580940del
  • NC_000007.13:g.2580939_2580940delCT
  • NM_152743.3:c.1313_1314del
  • NM_152743.3:c.1313_1314delAG
  • NR_146879.2:n.1372_1373del
Protein change:
Q263fs
Links:
dbSNP: rs749240175
NCBI 1000 Genomes Browser:
rs749240175
Molecular consequence:
  • NM_001350626.2:c.1313_1314del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350627.2:c.788_789del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_152743.4:c.1313_1314del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_146879.2:n.1372_1373del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL)
Identifiers:
MONDO: MONDO:0013784; MedGen: C3281029; Orphanet: 435845; OMIM: 614498

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000652222Invitaecriteria provided, single submitter
Pathogenic
(Sep 29, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000778422Equipe Genetique des Anomalies du Developpement, Université de Bourgognecriteria provided, single submitter
Pathogenic
(Apr 14, 2017)
inheritedclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedinheritedyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Lethal neonatal rigidity and multifocal seizure syndrome--report of another family with a BRAT1 mutation.

Straussberg R, Ganelin-Cohen E, Goldberg-Stern H, Tzur S, Behar DM, Smirin-Yosef P, Salmon-Divon M, Basel-Vanagaite L.

Eur J Paediatr Neurol. 2015 Mar;19(2):240-2. doi: 10.1016/j.ejpn.2014.11.004. Epub 2014 Nov 29.

PubMed [citation]
PMID:
25500575

BRAT1 mutations present with a spectrum of clinical severity.

Srivastava S, Olson HE, Cohen JS, Gubbels CS, Lincoln S, Davis BT, Shahmirzadi L, Gupta S, Picker J, Yu TW, Miller DT, Soul JS, Poretti A, Naidu S.

Am J Med Genet A. 2016 Sep;170(9):2265-73. doi: 10.1002/ajmg.a.37783. Epub 2016 Jun 9. Review.

PubMed [citation]
PMID:
27282546
PMCID:
PMC5532882
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000652222.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change deletes 2 nucleotides from exon 9 of the BRAT1 mRNA (c.1313_1314delAG), causing a frameshift at codon 438. This creates a premature translational stop signal (p.Gln438Argfs*51) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in BRAT1 are known to be pathogenic (PMID: 25500575, 27282546). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000778422.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

Last Updated: May 10, 2021

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