BRCA2 N372H - GET-Evidence



(BRCA2 Asn372His)

Short summary

This is a common variant of BRCA2 (HapMap allele frequency of 23%). The variant is weakly associated with an increased chance of breast cancer, and zygosity of the variant is associated with sex of children: male children are more likely to be homozygous for this variant, female children are more likely to be heterozygous.

Variant evidence

Gene is associated with breast cancer, but polyphen predicts benign effect

Functional -
Case/Control 2

p = 0.026

See Healey CS et al. 2000 (11062481).

Clinical importance
Severity 4

Breast cancer is potentially lethal

Treatability 3

Screening and treatment may reduce mortality

Penetrance 2

2% attributable risk

See Healey CS et al. 2000 (11062481).



Low clinical importance, Uncertain pathogenic

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

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • C @ chr13:32906729: 23.7% (2517/10640) in EVS
  • C @ chr13:31804728: 23.4% (30/128) in GET-Evidence
  • Frequency shown in summary reports: 23.7% (2517/10640)


Healey CS, Dunning AM, Teare MD, Chase D, Parker L, Burn J, Chang-Claude J, Mannermaa A, Kataja V, Huntsman DG, Pharoah PD, Luben RN, Easton DF, Ponder BA. A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability. Nat Genet. 2000 Nov;26(3):362-4. PubMed PMID: 11062481.

Combining five case-control studies (three British, one German, one Finnish) they find that homozygousity for this variant is associated with increased breast cancer risk with OR=1.3, p=0.026. They estimate that the population attributable risk of breast cancer due to N372H is ~2% (0.48-3.34 95% confidence).

Deviation from Hardy-Weinberg equilibrium (the expected distribution of heterozygotes and homozygotes) caused them to investigate and find that there is a reduced rate of homozygous females (0.82 fitness relative to heterozygous) and an increased rate of heterozygous. Testing newborns they conclude that this difference is occurring prior to birth — females have an excess of heterozygotes and deficit of homozygotes (p=0.06), males have an excess of homozygotes and a deficit of heterozygotes (p=0.001).

Teare MD, Cox A, Shorto J, Anderson C, Bishop DT, Cannings C. Heterozygote excess is repeatedly observed in females at the BRCA2 locus N372H. J Med Genet. 2004 Jul;41(7):523-8. PubMed PMID: 15235023; PubMed Central PMCID: PMC1735827.



hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het C @ chr13:32906729


hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het C @ chr13:32906729


hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het C @ chr13:32906729


hu0D879F - CGI sample GS00253-DNA_G01_200_37
het C @ chr13:32906729


hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het C @ chr13:32906729



hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het C @ chr13:32906729




hu3CAB43 - CGI sample GS01175-DNA_D03 from PGP sample 27486199
hom C @ chr13:32906729


hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het C @ chr13:32906729


hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het C @ chr13:32906729


huAE6220 - CGI sample GS00253-DNA_H01_200_37
hom C @ chr13:32906729


huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het C @ chr13:32906729


huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het C @ chr13:32906729


huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
het C @ chr13:32906729


GS06985 - var-GS06985-1100-36-ASM
het C @ chr13:31804729


GS07357 - var-GS07357-1100-36-ASM
het C @ chr13:31804729


GS12004 - var-GS12004-1100-36-ASM
het C @ chr13:31804729


GS18504 - var-GS18504-1100-36-ASM
het C @ chr13:31804729


GS18526 - var-GS18526-1100-36-ASM
het C @ chr13:31804729


GS18558 - var-GS18558-1100-36-ASM
het C @ chr13:31804729


GS18956 - var-GS18956-1100-36-ASM
het C @ chr13:31804729


GS19020 - var-GS19020-1100-36-ASM
het C @ chr13:31804729


GS19129 - var-GS19129-1100-36-ASM
het C @ chr13:31804729


GS19700 - var-GS19700-1100-36-ASM
het C @ chr13:31804729


GS19703 - var-GS19703-1100-36-ASM
het C @ chr13:31804729


GS19735 - var-GS19735-1100-36-ASM
het C @ chr13:31804729


GS20502 - var-GS20502-1100-36-ASM
het C @ chr13:31804729


GS20509 - var-GS20509-1100-36-ASM
het C @ chr13:31804729


GS21767 - var-GS21767-1100-36-ASM
het C @ chr13:31804729




Other external references

  • rs144848
  • GeneTests records for the BRCA2 gene
    Prostate cancer
    Fanconi Anemia
    BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer
    BRCA2 Hereditary Breast/Ovarian Cancer
    BRCA2-Related Fanconi Anemia

Other in silico analyses

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 4

Edit history

Gene search

"GENE" or "GENE A123C":

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