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PALB2

From SNPedia

is agene
is mentioned by
Full namepartner and localizer of BRCA2
EntrezGene79728
PheGenI79728
VariationViewer79728
ClinVarPALB2
GeneCardsPALB2
dbSNP79728
DiseasesPALB2
SADR79728
HugeNav79728
wikipediaPALB2
googlePALB2
gopubmedPALB2
EVSPALB2
HEFalMpPALB2
MyGene2PALB2
23andMePALB2
UniProtQ86YC2
EnsemblENSG00000083093
OMIM610355
# SNPs297
 Max MagnitudeChromosome positionSummary
i400048823,646,275
rs1057517539023,629,214
rs1057517563023,603,595
rs1057517585023,641,155
rs1057517600023,607,958
rs1057517602023,630,316
rs1057520645023,630,470
rs1057520653023,635,108
rs1057520736023,635,098
rs1060499812023,635,507
rs1060499813023,635,496
rs1060499814023,638,069
rs1060499817023,634,954
rs1060499818023,630,336
rs1060499819023,630,062
rs1060499821023,626,234
rs1060499823023,624,011
rs1060499824023,623,115
rs1060499827023,608,014
rs1060499828023,607,903
rs1060499829023,641,109
rs1060499830023,635,787
rs1060499831023,635,615
rs1060502726023,626,273
rs1060502734023,634,872
rs1060502738023,635,994
rs1060502748023,629,779
rs1060502759023,630,447
rs1060502760023,636,191
rs1060502761023,635,111
rs1060502764023,603,671
rs1060502769023,635,851
rs1060502771023,630,098
rs1060502772023,635,613
rs1060502781023,623,029
rs1060502785023,635,180
rs1060502787023,626,399
rs1060502788023,635,498
rs1060502800023,635,592
rs1060502803023,630,412
rs1060502804023,624,095
rs1060502805023,634,993
rs1064793220023,635,081
rs1064793772023,637,898
rs1064793827023,629,879
rs1064793869023,626,349
rs1064795168023,635,478
rs1064795640023,636,318
rs1064795824023,623,087
rs1064795953023,635,998
... 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