NM_152743.4(BRAT1):c.1499-1G>T AND Rigidity and multifocal seizure syndrome, lethal neonatal

Clinical significance:Pathogenic (Last evaluated: Apr 14, 2020)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001260917.1

Allele description [Variation Report for NM_152743.4(BRAT1):c.1499-1G>T]

NM_152743.4(BRAT1):c.1499-1G>T

Gene:
BRAT1:BRCA1 associated ATM activator 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Preferred name:
NM_152743.4(BRAT1):c.1499-1G>T
HGVS:
  • NC_000007.14:g.2539643C>A
  • NG_032167.1:g.21116G>T
  • NM_001350626.2:c.1499-1G>T
  • NM_001350627.2:c.974-1G>T
  • NM_152743.4:c.1499-1G>TMANE SELECT
  • NC_000007.13:g.2579277C>A
Functional consequence:
cryptic splice acceptor activation [Variation Ontology: 0375]
Observations:
1

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
SCV001237446Dr Sami Ulus Medical Genetics Department,Dr Sami Ulus Training and Research Hospital for Maternity and Children's Health and Diseasesno assertion criteria providedPathogenic
(Apr 14, 2020)
inheritedclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Turkishinheritedyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Dr Sami Ulus Medical Genetics Department,Dr Sami Ulus Training and Research Hospital for Maternity and Children's Health and Diseases, SCV001237446.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Turkish1not providednot providedclinical testingnot provided

Description

This mutation was not found in publicly available databases, including gnomAD database or among our in-house control clinical exomes. In silico predictions indicating that the variant is probably pathogenic by affecting pre-mRNA splicing were verified by genetic analysis based on reverse transcription of the patient's RNA followed by PCR amplifications and Sanger sequencing performed on cDNA. Sanger sequencing of cDNA revealed that the c.1499-1G>T variant disrupts the original acceptor splice site and activates a cryptic splice site only two nucleotides downstream of the pathogenic variant site. This change causes the deletion of the first two nucleotides of exon 12, leading to a frameshift (Glu500Alafs*36) in the mRNA of the BRAT1.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1inheritedyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 22, 2020

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