PMS2 P470S - GET-Evidence

Curation:
Currentness:

PMS2 P470S

(PMS2 Pro470Ser)


Short summary

Benign, common variant.

Variant evidence
Computational 1

Polyphen 2 predicts benign effect.

Functional -
Case/Control 5

High allele frequency strongly contradicts a pathogenic effect.

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Likely benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr7:6026988: 37.5% (4033/10758) in EVS
  • A @ chr7:5993513: 32.5% (41/126) in GET-Evidence
  • Frequency shown in summary reports: 37.5% (4033/10758)

Publications
 

Nakagawa H, Lockman JC, Frankel WL, Hampel H, Steenblock K, Burgart LJ, Thibodeau SN, de la Chapelle A. Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Cancer Res. 2004 Jul 15;64(14):4721-7. PubMed PMID: 15256438.

The authors note that, because of high population frequency, this and some other PMS2 variants obviously unrelated to disease.

Genomes
 

 

hu034DB1

 

hu04FD18

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr7:6026988

 

 

 

 

 

 

 

 

 

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het A @ chr7:6026988

 

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
hom A @ chr7:6026988

 

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr7:6026988

 

 

GS06994 - var-GS06994-1100-36-ASM
het A @ chr7:5993514

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr7:5993514

 

GS18501 - var-GS18501-1100-36-ASM
het A @ chr7:5993514

 

GS18502 - var-GS18502-1100-36-ASM
het A @ chr7:5993514

 

GS18508 - var-GS18508-1100-36-ASM
het A @ chr7:5993514

 

GS18537 - var-GS18537-1100-36-ASM
het A @ chr7:5993514

 

GS18558 - var-GS18558-1100-36-ASM
het A @ chr7:5993514

 

GS18940 - var-GS18940-1100-36-ASM
het A @ chr7:5993514

 

GS18942 - var-GS18942-1100-36-ASM
hom A @ chr7:5993514

 

GS18956 - var-GS18956-1100-36-ASM
hom A @ chr7:5993514

 

GS19017 - var-GS19017-1100-36-ASM
het A @ chr7:5993514

 

GS19238 - var-GS19238-1100-36-ASM
het A @ chr7:5993514

 

GS19240 - var-GS19240-1100-36-ASM
het A @ chr7:5993514

 

GS19648 - var-GS19648-1100-36-ASM
het A @ chr7:5993514

 

GS19649 - var-GS19649-1100-36-ASM
het A @ chr7:5993514

 

GS19669 - var-GS19669-1100-36-ASM
het A @ chr7:5993514

 

GS19670 - var-GS19670-1100-36-ASM
het A @ chr7:5993514

 

GS19701 - var-GS19701-1100-36-ASM
het A @ chr7:5993514

 

GS19704 - var-GS19704-1100-36-ASM
het A @ chr7:5993514

 

GS19834 - var-GS19834-1100-36-ASM
het A @ chr7:5993514

 

GS20502 - var-GS20502-1100-36-ASM
het A @ chr7:5993514

 

GS20509 - var-GS20509-1100-36-ASM
hom A @ chr7:5993514

 

GS21767 - var-GS21767-1100-36-ASM
het A @ chr7:5993514

 

NA12878

 

Other external references
 

    dbSNP
  • rs1805321
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the PMS2 gene
    Turcot Syndrome
    Hereditary Non-Polyposis Colon Cancer
    PMS2-Related Hereditary Non-Polyposis Colon Cancer
    PMS2-Related Turcot Syndrome
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PMS2
    PolyPhen-2
  • Score: 0.006 (benign)
    Web search results (4 hits -- see all)
  • Mismatch Repair Gene PMS2: Disease-Causing Germline Mutations ...
    These mutations abrogated PMS2 protein in germline cells by Western analysis. ... mutations (S46I and E541K on one chromosome; P470S on the other) ...
    cancerres.aacrjournals.org/cgi/content/full/64/14/4721
  • PolyPhen: results for P54278 P470S
    PMS1 PROTEIN HOMOLOG 2 (DNA MISMATCH REPAIR PROTEIN PMS2) ... Mapping of the substitution site to known protein 3D structures. Database. Initial number ...
    tux.embl-heidelberg.de/ramensky/data/html/SNP000064711.html
  • GENETICS OF PRIMARY ALDOSTERONISM – FAMILIAL ...
    For PMS2, 11 SNPs were found [two in the proximal promoter: -195T/C and -154C/G; four non-synonymous coding SNPs: C1408T (P470S), C1454A (T485K) ...
    espace.library.uq.edu.au/view/UQ:158577
  • DNA Repair Mechanisms in C. elegans
    ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag. van de ... Homologues for human MSH2, MSH6, MLH1, and PMS2 are present. ...
    igitur-archive.library.uu.nl/dissertations/.../brouwer.pdf

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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