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NM_000059.4(BRCA2):c.9006A>T (p.Glu3002Asp) AND not provided

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 16, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000656809.2

Allele description [Variation Report for NM_000059.4(BRCA2):c.9006A>T (p.Glu3002Asp)]

NM_000059.4(BRCA2):c.9006A>T (p.Glu3002Asp)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.9006A>T (p.Glu3002Asp)
Other names:
p.E3002D:GAA>GAT
HGVS:
  • NC_000013.11:g.32379802A>T
  • NG_012772.3:g.69323A>T
  • NM_000059.4:c.9006A>TMANE SELECT
  • NP_000050.2:p.Glu3002Asp
  • NP_000050.3:p.Glu3002Asp
  • LRG_293t1:c.9006A>T
  • LRG_293:g.69323A>T
  • LRG_293p1:p.Glu3002Asp
  • NC_000013.10:g.32953939A>T
  • NM_000059.3:c.9006A>T
  • U43746.1:n.9234A>T
  • p.E3002D
Nucleotide change:
9234A>T
Protein change:
E3002D
Links:
dbSNP: rs80359153
NCBI 1000 Genomes Browser:
rs80359153
Molecular consequence:
  • NM_000059.4:c.9006A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000108643GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))
Uncertain significance
(Oct 16, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000108643.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted BRCA2 c.9006A>T at the cDNA level, p.Glu3002Asp (E3002D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAA>GAT). Using alternate nomenclature, this variant would be defined as BRCA2 9234A>T. This variant has been reported to disrupt an exonic splicing enhancer (ESE) and to strengthen a cryptic acceptor site that is 51 nucleotides downstream of the canonical acceptor site, resulting in the production of both the canonical transcript (69%) as well as aberrant transcripts (31%) (Acedo 2012). Fackenthal et al. (2016) demonstrated that use of this cryptic acceptor site may be a naturally occurring transcript, observed at minor frequencies. BRCA2 Glu3002Asp was shown to have mild to moderate effects on BRCA2 and Filamin A interaction, cellular multinucleation, unresolved cytoplasmic bridges, and homology-directed DNA break repair (HDR) activity; a multifactorial likelihood model calculated its probability of neutrality as 0.94 (Mondal 2012, Guidugli 2013). BRCA2 Glu3002Asp was not observed in large population cohorts (Lek 2016). Since Glutamic Acid and Aspartic Acid share similar properties, this is considered a conservative amino acid substitution. BRCA2 Glu3002Asp occurs at a position that is conserved across species and is located in the DNA binding domain (Borg 2010). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information and internal data, it is unclear whether BRCA2 Glu3002Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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

Last Updated: Sep 29, 2024