PALB2 E672Q - GET-Evidence

Curation:
Currentness:

PALB2 E672Q

(PALB2 Glu672Gln)


Short summary

Probably benign.

Variant evidence
Computational

Polyphen 2 predicts damaging effect, but Rahman et al. conclude that missense variants in general have no evidence for increased incidence of breast cancer & similar appears to be true for recessive Fanconi Anemia mutations in the gene.

Functional -
Case/Control 4

Same frequency in breast cancer cases and controls.

See Rahman N et al. 2007 (17200668).

Familial

No familial data

 
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

  • G @ chr16:23641461: 2.4% (263/10758) in EVS
  • G @ chr16:23548961: 0.8% (1/128) in GET-Evidence
  • Frequency shown in summary reports: 2.4% (263/10758)

Publications
 

Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D; Breast Cancer Susceptibility Collaboration (UK), Easton DF, Stratton MR. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007 Feb;39(2):165-7. Epub 2006 Dec 31. PubMed PMID: 17200668; PubMed Central PMCID: PMC2871593.

This paper examines PALB2 heterozygous mutations for increased risk of breast cancer and finds that truncating mutations (nonsense or frameshift) confer increased risk of breast cancer. This variant (E672Q) is reported as a fairly common substitution variant that was equally common in cases and control alleles ( 49/1846 = 2.7% vs. 65/2168 = 3.0%, respectively), and the authors conclude that there is no evidence that this or other missense variants (especially those with >1% freq) are breast cancer susceptibility alleles.

Genomes
 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het G @ chr16:23641461

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het G @ chr16:23641461

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het G @ chr16:23641461

 

huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
het G @ chr16:23641461

 

GS21767 - var-GS21767-1100-36-ASM
het G @ chr16:23548962

 

Other external references
 

    dbSNP
  • rs45532440
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.952 (probably damaging)

Other in silico analyses
 

  • NBLOSUM100 score = –2
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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