BRCA1 R1347G - GET-Evidence

Curation:
Currentness:

BRCA1 R1347G

(BRCA1 Arg1347Gly)


Short summary

Believed to be a nonpathogenic polymorphism, although Polyphen 2 predicts a damaging effect.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 2

No statistically significant difference between patient and control populations

See Deffenbaugh AM et al. 2002 (12215251).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr17:41243509: 0.4% (46/10758) in EVS
  • C @ chr17:38497034: 2.3% (3/128) in GET-Evidence
  • Frequency shown in summary reports: 0.4% (46/10758)

Publications
 

Durocher F, Shattuck-Eidens D, McClure M, Labrie F, Skolnick MH, Goldgar DE, Simard J. Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense mutations in unaffected and breast/ovarian cancer populations. Hum Mol Genet. 1996 Jun;5(6):835-42. PubMed PMID: 8776600.

These authors report this variant in 1 of 114 cases and 0 out of 232 controls, they are inconclusive regarding whether it is pathogenic. The allele frequency seems a bit low compared to other reports.

Deffenbaugh AM, Frank TS, Hoffman M, Cannon-Albright L, Neuhausen SL. Characterization of common BRCA1 and BRCA2 variants. Genet Test. 2002 Summer;6(2):119-21. PubMed PMID: 12215251.

(Based on the abstract) These authors conclude this variant (among a set of others) is not deleterious, based on “epidemiological and biological criteria”. It had not statistically significant difference between patient and control populations.

Genomes
 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het C @ chr17:41243509

 

GS19648 - var-GS19648-1100-36-ASM
het C @ chr17:38497035

 

GS20509 - var-GS20509-1100-36-ASM
het C @ chr17:38497035

 

Other external references
 

    dbSNP
  • rs28897689
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the BRCA1 gene
    BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer
    BRCA1 Hereditary Breast/Ovarian Cancer
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/BRCA1
    PolyPhen-2
  • Score: 0.991 (probably damaging)
    Web search results (32 hits -- see all)
  • BRCA1 UVs
    BRCA1. 8. 613. T to C. 165. Leu to Pro. L165P. Nee. 1. BRCA1. 10. 760. A to G. 214 ... 1. BRCA1. 11. 4158. A to G. 1347. Arg to Gly. 4158A/G (R1347G) Ja. 8. BRCA1. 13 ...
    www.humgen.nl/lab-devilee/UncVar/B1UVs.htm
  • Characterization of common BRCA1 and BRCA2 variants.
    2002 Summer;6(2):119-21. Characterization of common BRCA1 and BRCA2 variants. ... therefore conclude that the BRCA1 missense mutations R1347G, S1512I ...
    www.ncbi.nlm.nih.gov/pubmed/12215251
  • Comparison of BRCA1 polymorphisms, rare sequence variants and ...
    The BRCA1 gene contains 5592 bp of coding sequence encompassed within 22 exons spread ... as of the R1347G mutation on the BRCA1 activity when a functional ...
    hmg.oxfordjournals.org/cgi/content/full/5/6/835
  • A Multi-Exonic BRCA1 Deletion Identified in Multiple Families ...
    A Multi-Exonic BRCA1 Deletion Identified in Multiple Families through ... identified a novel 26-kb deletion of BRCA1 exons 14 through 20 in patients from ...
    jmd.amjpathol.org/cgi/content/full/7/1/139
  • A Multi-Exonic BRCA1 Deletion Identified in Multiple Families ...
    deletion of BRCA1 exons 14 through 20 in patients. from multiple families with hereditary ... Figure 2. Schematic diagram of relevant regions of the BRCA1 locus. ...
    jmd.amjpathol.org/cgi/reprint/7/1/139.pdf
  • Selecting for BRCA1 testing using a combination of ...
    BRCA1 gene-related tumours are more frequently estrogen receptor (ER) ... The BRCA1 molecular analysis, including Multiplex Ligation-dependent Probe ...
    biomedcentral.com/content/download/xml/1471-2407-9-360.xml
  • Comparison of BRCA1 polymorphisms, rare sequence variants and ...
    Inherited mutations in the BRCA1 gene are known to confer a predisposition to breast and ovarian cancer. ... missense mutations M1008I, E1219D, R1347G, T1561I and M1628V were ...
    www.ihop-net.org/UniPub/iHOP/gp/739851.html
  • MJM FOCUS
    attributed to BRCA1 and BRCA2, options for cancer. prevention and ... In carriers of BRCA1 or BRCA2 mutations, estimates of the cumulative lifetime risk, by ...
    www.medicine.mcgill.ca/mjm/v06n02/page 129-142.PDF
  • 0108049
    mutations of BRCA1 are predicted to result in gross truncation ... and R1347G). None of the. mutants in this group significantly affects BRCA1-mediated ...
    www.broadinstitute.org/~anne/publications/Ye.pdf
  • Conservation of the BRCA1 Gene
    Title of thesis: Conservation of the BRCA1 Gene. Name of author: Matthew Gary Wronkowski ... R1347G | 149. R841W | 114. M1008I | 105. 4184del4 | 105. R1443X | 103 ...
    www.csh.rit.edu/~mattw/thesis/mwronkow-thesis-final.pdf

Other in silico analyses
 

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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