NM_000059.3(BRCA2):c.5200dup (p.Glu1734fs) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 6, 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:
RCV000588702.4

Allele description [Variation Report for NM_000059.3(BRCA2):c.5200dup (p.Glu1734fs)]

NM_000059.3(BRCA2):c.5200dup (p.Glu1734fs)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.5200dup (p.Glu1734fs)
HGVS:
  • NC_000013.11:g.32339555dup
  • NG_012772.3:g.29076dup
  • NM_000059.3:c.5200dup
  • NP_000050.2:p.Glu1734fs
  • LRG_293t1:c.5200dup
  • LRG_293:g.29076dup
  • LRG_293p1:p.Glu1734fs
  • NC_000013.10:g.32913691_32913692insG
  • NC_000013.10:g.32913692dup
  • NM_000059.3:c.5200dupG
Protein change:
E1734fs
Links:
dbSNP: rs1555284103
NCBI 1000 Genomes Browser:
rs1555284103
Molecular consequence:
  • NM_000059.3:c.5200dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000694840Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Jun 12, 2017)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000758817Invitaecriteria provided, single submitter
Pathogenic
(Mar 6, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

LOVD v.2.0: the next generation in gene variant databases.

Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT.

Hum Mutat. 2011 May;32(5):557-63. doi: 10.1002/humu.21438. Epub 2011 Feb 22.

PubMed [citation]
PMID:
21520333

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]
PMID:
20104584
PMCID:
PMC2928257
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694840.1

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

Description

Variant summary: The BRCA2 c.5200dupG (p.Glu1734Glyfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5217_5220delTTTA, p.Tyr1739X; c.5238dupT, p.Asn1747X; c.5290_5291delTC, p.Ser1764fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 119462 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.

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

From Invitae, SCV000758817.4

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

Description

This sequence change creates a premature translational stop signal (p.Glu1734Glyfs*9) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 495468). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Aug 17, 2021

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