ERCC6 R1213G - GET-Evidence

Curation:
Currentness:

ERCC6 R1213G

(ERCC6 Arg1213Gly)


Short summary

When homozygous, this variant may cause Cockayne Syndrome, which is a severe autosomal-recessive disorder characterized by abnormal early growth and development, abnormal sensitivity to sunlight, and premature aging. Cockayne Syndrome Type I and Type II lead to death in early childhood. Several other variants in the ERCC6 gene are linked to Cockayne Syndrome. This variant may also be linked to age-related macular degeneration like other ERCC6 variants, and has been linked to colorectal cancer in one study.

Variant evidence
Computational 3

NBLOSUM score of 6, PolyPhen damaging prediction, other variants in this gene cause Cockayne Syndrome and Age-related macular degeneration.

Functional 1

One study shows this variant causing Cockayne Syndrome.

Case/Control

No case/control studies have been done on this variant’s relationship to Cockayne Syndrome at this time.

Familial

No familial studies have been done on this variant’s relationship to Cockayne Syndrome at this time.

 
Clinical importance
Severity 5

Cockayne Syndrome (CS) is a serious condition that is characterized by abnormal early growth and development. There are three types that range in severity, but both Type I and Type II cause death in childhood.

Treatability 1

There is no cure for CS, but for as long as an affected person is living the issues that develop as a consequence of the condition (i.e. cataracts, hearing loss) can be managed.

Penetrance

Cannot be assessed based on the literature at this time.

 

Impact

Low clinical importance, Uncertain pathogenic

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

Inheritance pattern

recessive

Summary of published research, and additional commentary

Only one study has shown the connection between this variant and Cockayne Syndrome in a Type III individual with onset of the disease at age 2 (See Mallery et al 1998 http://www.sciencedirect.com/science/article/pii/S0002929707601256). Several other studies on similar missense mutations in the ERRC6 gene have demonstrated a connection to Cockayne Syndrome. All studies done on this variant at this time are individual, but in this individual studies it has been linked to susceptibility to colorectal cancer, laryngeal cancer, and to the increased risk for breast cancer for smokers.

Allele frequency

  • C @ chr10:50678369: 19.7% (2118/10758) in EVS
  • C @ chr10:50348374: 18.0% (23/128) in GET-Evidence
  • Frequency shown in summary reports: 19.7% (2118/10758)

Publications
 

Genomes
 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het C @ chr10:50678369

 

 

 

hu4CA5B9 - CGI sample GS01669-DNA_B03 from PGP sample 14427241
het C @ chr10:50678369

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het C @ chr10:50678369

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
het C @ chr10:50678369

 

hu7A4AD1 - CGI sample GS01669-DNA_C05 from PGP sample 42408046
het C @ chr10:50678369

 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het C @ chr10:50678369

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het C @ chr10:50678369

 

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het C @ chr10:50678369

 

GS07357 - var-GS07357-1100-36-ASM
het C @ chr10:50348375

 

GS12004 - var-GS12004-1100-36-ASM
het C @ chr10:50348375

 

GS18501 - var-GS18501-1100-36-ASM
het C @ chr10:50348375

 

GS18504 - var-GS18504-1100-36-ASM
het C @ chr10:50348375

 

GS18537 - var-GS18537-1100-36-ASM
het C @ chr10:50348375

 

GS18940 - var-GS18940-1100-36-ASM
het C @ chr10:50348375

 

GS18956 - var-GS18956-1100-36-ASM
het C @ chr10:50348375

 

GS19025 - var-GS19025-1100-36-ASM
het C @ chr10:50348375

 

GS19670 - var-GS19670-1100-36-ASM
het C @ chr10:50348375

 

GS19700 - var-GS19700-1100-36-ASM
het C @ chr10:50348375

 

GS19703 - var-GS19703-1100-36-ASM
het C @ chr10:50348375

 

GS19834 - var-GS19834-1100-36-ASM
het C @ chr10:50348375

 

Other external references
 

    dbSNP
  • rs2228527
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the ERCC6 gene
    Age-related macular degeneration
    Cockayne Syndrome
    Age-Related Macular Degeneration 5
    Cockayne Syndrome Type B
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ERCC6
    PolyPhen-2
  • Score: 0.957 (probably damaging)
    Web search results (20 hits -- see all)
  • Genetic variation in the DNA repair genes is predictive of ...
    complementing, group 6 (ERCC6) were associated with differ ... other variants such as EXO1 E670G, ERCC6 R1213G, POLB. P242R, POLQ T1117R, BLM P868I and ...
    hmg.oxfordjournals.org/cgi/reprint/16/19/2333.pdf
  • Publications Search
    The ERCC6 1213G variant, which is thought to reduce NER capacity, was associated ... When the combined effects of ERCC6 R1213G and XPC R492H were examined, the risk ...
    dceg2.cancer.gov/cgi-bin-pubsearch/pubsearch/index.pl?...
  • Genetic variation in the DNA repair genes is predictive of ...
    Carrier status for ERCC6 399D was associated with poorer prognosis ... other variants such as EXO1 E670G, ERCC6 R1213G, POLB P242R, POLQ T1117R, BLM P868I and ...
    hmg.oxfordjournals.org/cgi/content/full/16/19/2333
  • Molecular epidemiology of colorectal cancer
    I N S T I T U T E O F C A N C E R E P I D E M I O L O G Y. N A T I O N A L R E S E A R C H ... E N V I R O N M E N T. RIKKE DALGAARD HANSEN. MOLECULAR EPIDEMIOLOGY OF ...
    www.arbejdsmiljoforskning.dk/upload/rha_phd.pdf
  • Molecular Analysis of Mutations in the CSB (ERCC6) Gene in ...
    nated "ERCC6" was cloned by its ability to correct the. UV sensitivity of a mutant hamster ... R670W, W851R, V957G, P1042L, or R1213G. In contrast, when the cDNA ...
    sciencedirect.com/science?_ob=MImg&...&ie=/sdarticle.pdf
  • NUCELOTIDE EXCISION REPAIR AND PROSTATE CANCER RISK
    ERCC6/ CSB/ CKN2. Excision repair cross- complementing rodent. repair deficiency, ... R1213G. R1230P. L1308V. Q1413R. 2228528. 2228526. 2228527. 4253211. 2229761 ...
    www1.elsevier.com/homepage/sab/oncoserve/cl_mr/hu.pdf
  • UNIVERZITA KARLOVA V PRAZE
    predispozície vzniku kolorektálnej rakoviny" spracovala sam ostatne s ... Pri sledovaní kombinovaného efektu CSB R1213G. a XPC G492A polymorfných miest sa zistilo, ...
    web.natur.cuni.cz/cellbiol/.../112_bp_Zivcakova_2009.pdf
  • Table S1.
    R1213G. R1213G. Mallery, 1998. CS8BR. Q854* Q854* Mallery, 1998. UVS1KO ... analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome. ...
    plosgenetics.org/article/...

Other in silico analyses
 

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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