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PALB2

From SNPedia

is agene
is mentioned by
Full namepartner and localizer of BRCA2
EntrezGene79728
PheGenI79728
VariationViewer79728
ClinVarPALB2
GeneCardsPALB2
dbSNP79728
SADR79728
HugeNav79728
wikipediaPALB2
googlePALB2
gopubmedPALB2
EVSPALB2
HEFalMpPALB2
MyGene2PALB2
23andMePALB2
UniProtQ86YC2
EnsemblENSG00000083093
OMIM610355
# SNPs215
 Max MagnitudeChromosome positionSummary
i400048823,646,275
rs118203997723,634,893
rs118203998723,603,471
rs118203999723,623,003
rs152451023,634,870
rs16940342023,633,265
rs180177083723,637,865
rs180177084723,636,317
rs180177085723,636,151
rs180177090723,635,849
rs180177091723,635,795
rs180177092723,635,788
rs180177097723,635,519
rs180177098723,635,495
rs180177099723,635,489
rs180177100723,635,306
rs180177102723,634,954
rs180177103723,634,913
rs180177110323,629,897
rs180177111723,629,831
rs180177112723,629,768
rs180177113723,629,760
rs180177115223,629,231
rs180177116723,629,269
rs180177121723,626,297
rs180177122723,626,266
rs180177124723,624,082
rs180177126723,623,044
rs180177127723,622,982
rs180177131723,621,449
rs180177132723,621,362
rs180177133723,614,089
rs180177134723,607,916
rs180177135723,607,891
rs180177136723,607,860
rs180177138723,603,523
rs180177142323,638,106
rs180177143723,637,886
rs24993523,613,903
rs2499541.223,629,146
rs309614523,601,679
rs4202591.923,622,705
rs447529023,622,102
rs45476495023,626,310
rs45551636123,622,972
rs515726060723,635,493
rs515726065723,635,232
rs515726067723,635,229
rs515726071723,635,067
rs515726073723,634,869
... further results

This gene plays a role in breast cancer and Fanconi anemia, complementation group N.

PALB2 (Partner and Localizer of BRCA2) is a tumor suppressor gene encoding the PALB2 protein. The PALB2 protein binds and stabilizes the BRCA2 protein, allowing it to repair DNA in the same DNA damage response pathway as BRCA1. Single allele germline loss-of-function mutations in PALB2 are associated with an increased risk of breast cancer and pancreatic cancer, and biallelic mutations lead to a Fanconi anemia complementation group, [FANCN]]. PALB2 mutations have intermediate penetrance, with carriers having about a two- to four-fold increased risk of developing breast cancer compared with the general population. These risk estimates may be higher in patients with a family history of breast cancer.

PALB2 (partner and localizer of BRCA2) is a tumor suppressor gene which encodes for the PALB2 protein, which interacts with the protein produced by the BRCA2 gene. The PALB2 protein stabilizes the BRCA2 protein, allowing the BRCA2 protein to repair DNA double-strand breaks by a process known as homologous recombination. Monoallelic germline loss-of-function mutations in PALB2 are associated with an increased risk of breast and pancreatic cancer and biallelic mutations lead to a Fanconi anemia complementation group, designated subtype N (FANCN). Most pathogenic PALB2 mutations that have been detected are truncating frameshift or stop codons and are scattered throughout the entire gene region, without hot-spot areas.

[PMID 25099575] This paper 'Breast-Cancer Risk in Families with Mutations in PALB2' (N Engl J Med 2014; 371:497-506) analyzed the risk of breast cancer among 362 members of 154 families who had deleterious truncating, splice, or deletion mutations in PALB2. The age-specific breast-cancer risk for mutation carriers was estimated with the use of a modified segregation-analysis approach that allowed for the effects of PALB2 genotype and residual familial aggregation. The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% (95% confidence interval [CI], 9 to 20) by 50 years of age and 35% (95% CI, 26 to 46) by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort (P<0.001) and by other familial factors (P=0.04). The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25 to 44) for those with no family history of breast cancer to 58% (95% CI, 50 to 66) for those with two or more first-degree relatives with breast cancer at 50 years of age.

Based on the Supplementary data presented in [PMID 25099575], PALB2 SNPs implicated in risk for breast cancer include:

  • rs180177102 - the most common, apparently, even though even it is quite rare

and more exhaustively:

dbSNP rs-id Coding Change
rs587776405 c.48G>A
rs180177142 c.72del
rs587776406 c.156del
rs180177143 c.172_175del
rs180177083 c.196C>T
rs180177084 c.229del
rs587776407 c.451C>T
rs515726124 c.509_510del
rs180177092 c.757_758del
rs587776408 c.886del
rs587776409 c.956_962del
rs180177097 c.1027del
rs587776410 c.1037_1041del
rs587776411 c.1108C>T
rs180177100 c.1240C>T
rs515726065 c.1314del
rs587776412 c.1431del
rs587776413 c.1571C>G
rs587776414 c.1591_1600del
rs180177102 c.1592del
rs118203997 c.1653T>A
rs587776415 c.2074C>T
rs587776416 c.2167_2168del
rs180177110 c.2257C>T
rs180177111 c.2323C>T
rs180177112 c.2386G>T
rs587776417 c.2515-1G>T
rs180177116 c.2521del
rs180177121 c.2686dup
rs180177122 c.2718G>A
rs587776418 c.2787_2788del
rs587776419 c.2834+1G>T
rs515726099 c.2835-1G>C
rs587776420 c.2888del
rs587776421 c.2919_2920del
rs180177127 c.2982dup
rs587776422 c.3022del
rs180177132 c.3113G>A
rs180177133 c.3116del
rs587776423 c.3201+1G>C
rs180177135 c.3323del
rs587776424 c.3423_3426del
rs587776425 c.3426dup
rs587776426 c.3456dup
rs587776427 c.3497_3498del
rs587776428 c.3504_3505del
rs118203998 c.3549C>A, C>G
rs515726117 c.3362del