chr12:25398285:C>A Detail (hg19) (KRAS)

Information

Genome

Assembly Position
hg19 chr12:25,398,285-25,398,285
hg38 chr12:25,245,351-25,245,351 View the variant detail on this assembly version.

HGVS

Type Transcript Protein
RefSeq NM_004985.4:c.34G>T NP_004976.2:p.Gly12Cys
NM_033360.3:c.34G>T NP_203524.1:p.Gly12Cys
Ensemble ENST00000256078.10:c.34G>T ENST00000256078.10:p.Gly12Cys
Summary

MGeND

Clinical significance Pathogenic not provided
Variant entry 305
GWAS entry
Disease area statistics Show details

Frequency

JP HGVD:[No Data.]
ToMMo:[No Data.]
NCBN:[No Data.]
NCBN(Hondo):[No Data.]
NCBN(Ryukyu):[No Data.]
East asia ExAC:<0.001

Prediction

ClinVar

Clinical Significance Likely pathogenic
Review star
Show details
Links
Type Database ID Link
Gene MIM 190070 OMIM
HGNC 6407 HGNC
Ensembl ENSG00000133703 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC COSM1140136 COSMIC
MONDO
Disease area statistics
MGeND
Clinical significance Last evaluated Condition Origin Submission ID Submitter Institute Citation Comment Image
not provided fundus of stomach not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided body of stomach not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided jejunum not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided caecum not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided appendix not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided ascending colon not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided transverse colon not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided descending colon not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided sigmoid colon not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided colon, unspecified not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided malignant neoplasm of rectum not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided anal canal not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided extrahepatic bile duct not provided MGS000040
(TMGS000095) 		Hitoshi Nakagama National Cancer Center Japan
not provided Non-small cell lung cancer somatic MGS000026
(TMGS000046) 		Manabu Muto Kyoto University
Pathogenic Colorectal somatic MGS000038
(TMGS000091) 		Manabu Muto
Ichiro Kinoshita		 Kyoto University
Department of Medical Oncology Faculty of Medicine and Graduate School of Medicine Hokkaido University
Pathogenic Endometrial somatic MGS000038
(TMGS000091) 		Manabu Muto
Ichiro Kinoshita		 Kyoto University
Department of Medical Oncology Faculty of Medicine and Graduate School of Medicine Hokkaido University
not provided Carcinoma of bladder (disorder) unknown MGS000021
(TMGS000080) 		Manabu Muto Kyoto University
Pathogenic Others somatic MGS000038
(TMGS000091) 		Manabu Muto
Ichiro Kinoshita		 Kyoto University
Department of Medical Oncology Faculty of Medicine and Graduate School of Medicine Hokkaido University
Pathogenic Biliary somatic MGS000038
(TMGS000091) 		Manabu Muto
Ichiro Kinoshita		 Kyoto University
Department of Medical Oncology Faculty of Medicine and Graduate School of Medicine Hokkaido University
not provided Carcinoma of pancreas (disorder) unknown MGS000025
(TMGS000084) 		Manabu Muto Kyoto University
not provided Small bowel cancer (NEC) somatic MGS000018
(TMGS000110) 		Hitoshi Nakagama National Cancer Center Japan 30742731
not provided Non-small cell lung cancer somatic MGS000018
(TMGS000110) 		Hitoshi Nakagama National Cancer Center Japan 30742731
not provided colorectal cancer somatic MGS000018
(TMGS000110) 		Hitoshi Nakagama National Cancer Center Japan 30742731
not provided Small bowel cancer somatic MGS000018
(TMGS000110) 		Hitoshi Nakagama National Cancer Center Japan 30742731
not provided fundus of stomach not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided caecum not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided appendix not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided ascending colon not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided transverse colon not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided descending colon not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided sigmoid colon not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided colon, unspecified not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided malignant neoplasm of rectosigmoid junction not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided malignant neoplasm of rectum not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided intrahepatic bile duct carcinoma not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided head of pancreas not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided tail of pancreas not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided ill-defined sites within the digestive system not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided bronchus or lung, unspecified not provided MGS000042
(TMGS000093) 		Hitoshi Nakagama National Cancer Center Japan
not provided other somatic MGS000039
(TMGS000092) 		Hitoshi Nakagama National Cancer Center Japan 29659903
not provided jejunum not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided caecum not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided appendix not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided descending colon not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided colon, unspecified not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided malignant neoplasm of rectosigmoid junction not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided malignant neoplasm of rectum not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided anal canal not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided extrahepatic bile duct not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided ill-defined sites within the digestive system not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
not provided bronchus or lung, unspecified not provided MGS000041
(TMGS000094) 		Hitoshi Nakagama National Cancer Center Japan
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2001-09-15 no assertion criteria provided lung carcinoma somatic Detail
Pathogenic 2014-10-02 no assertion criteria provided Non-small cell lung carcinoma somatic Detail
not provided no assertion provided endometrial carcinoma somatic Detail
Pathogenic 2014-10-02 no assertion criteria provided Thyroid tumor somatic Detail
Pathogenic 2014-10-02 no assertion criteria provided Neoplasm of ovary somatic Detail
Pathogenic Likely pathogenic 2015-07-14 no assertion criteria provided lung adenocarcinoma somatic Detail
Pathogenic 2015-07-14 no assertion criteria provided Neoplasm of the large intestine somatic Detail
Pathogenic 2020-10-30 no assertion criteria provided gallbladder cancer somatic Detail
Pathogenic no assertion criteria provided not provided unknown Detail
Likely pathogenic 2023-02-23 criteria provided, single submitter RASopathy germline Detail
Likely pathogenic no assertion criteria provided lung cancer somatic Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
lung non-small cell carcinoma Selumetinib,Docetaxel B Predictive Supports Sensitivity/Response Somatic 3 26125448 Detail
cancer ARS-853,Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor D Predictive Supports Sensitivity/Response Somatic 3 26739882 Detail
colorectal cancer Gefitinib,Erlotinib B Predictive Supports Resistance Somatic 3 23313110 Detail
lung non-small cell carcinoma B Prognostic Supports Poor Outcome Somatic 3 22247021 Detail
colorectal cancer Dactolisib,Selumetinib D Predictive Supports Sensitivity/Response Somatic 2 22392911 Detail
colorectal cancer Panitumumab C Predictive Supports Resistance Somatic 18316791 Detail
lung cancer Gefitinib B Predictive Supports Resistance Somatic 2 17409929 Detail
multiple myeloma Melphalan B Predictive Supports Resistance Somatic 19284554 Detail
multiple myeloma Melphalan D Predictive Supports Resistance Somatic 2 11050000 Detail
multiple myeloma Melphalan D Predictive Supports Resistance Somatic 12483530 Detail
multiple myeloma Melphalan D Predictive Supports Resistance Somatic 2 16497971 Detail
lung cancer B Diagnostic Supports Positive Somatic 2 23014527 Detail
colorectal cancer Regorafenib D Predictive Supports Resistance Somatic 26161928 Detail
DisGeNET
Score Disease name Description Source Pubmed Links
0.385 Non-small cell lung carcinoma Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were i... BeFree 24200637 Detail
0.321 Non-small cell lung carcinoma Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were i... BeFree 24200637 Detail
0.256 Stomach Neoplasms NA CLINVAR Detail
0.256 ovarian neoplasm NA CLINVAR Detail
0.125 Malignant neoplasm of urinary bladder NA CLINVAR Detail
0.113 Malignant neoplasm of lung Gene-expression profiles in lung cancer cell lines and surgically resected lung ... BeFree 25170638 Detail
0.321 Non-small cell lung carcinoma The dominant role of G12C over other KRAS mutation types in the negative predict... BeFree 23313110 Detail
0.146 Adenocarcinoma of lung (disorder) Presence of the KRAS G12C mutation had 96% specificity and positive predictive v... BeFree 23887294 Detail
0.229 Carcinoma of lung Gene-expression profiles in lung cancer cell lines and surgically resected lung ... BeFree 25170638 Detail
0.146 Adenocarcinoma of lung (disorder) KRAS-G12C mutation is associated with poor outcome in surgically resected lung a... BeFree 25170638 Detail
0.229 Carcinoma of lung NA CLINVAR Detail
<0.001 neurilemmoma A KRAS G12S mutation was also evident in one sporadic schwannoma. BeFree 23190154 Detail
0.121 Squamous cell carcinoma of lung NA CLINVAR Detail
0.163 Neoplasm Metastasis Interestingly, during anti-EGFR treatment, it came to the selection of cells wit... BeFree 23606169 Detail
0.014 polyps There was a strong association between germinal MUTYH mutation and KRAS Gly12Cys... BeFree 24470512 Detail
<0.001 Follicular thyroid carcinoma Follicular carcinoma presenting as autonomous functioning thyroid nodule and con... BeFree 16756473 Detail
<0.001 Erdheim-Chester disease There was 100% concordance between tissue and urinary cfDNA genotype in treatmen... BeFree 25324352 Detail
0.003 Thyroid Nodule Follicular carcinoma presenting as autonomous functioning thyroid nodule and con... BeFree 16756473 Detail
0.385 Non-small cell lung carcinoma The dominant role of G12C over other KRAS mutation types in the negative predict... BeFree 23313110 Detail
0.321 Non-small cell lung carcinoma We selected NSCLC cell lines--A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H312... BeFree 22617245 Detail
0.455 Costello syndrome (disorder) We have observed unusual transverse distal phalangeal creases in two patients, o... BeFree 17324647 Detail
0.122 Costello syndrome (disorder) We have observed unusual transverse distal phalangeal creases in two patients, o... BeFree 17324647 Detail
0.265 Noonan syndrome We have observed unusual transverse distal phalangeal creases in two patients, o... BeFree 17324647 Detail
0.121 Noonan syndrome We have observed unusual transverse distal phalangeal creases in two patients, o... BeFree 17324647 Detail
0.121 Cardio-facio-cutaneous syndrome We have observed unusual transverse distal phalangeal creases in two patients, o... BeFree 17324647 Detail
0.130 endometrial carcinoma NA CLINVAR Detail
0.149 Carcinogenesis This system allowed us to rapidly compare the ability of 12 different KRAS mutat... BeFree 25065594 Detail
0.321 Non-small cell lung carcinoma NA CLINVAR Detail
0.448 juvenile myelomonocytic leukemia NA CLINVAR Detail
0.032 Malignant neoplasm of thyroid The effect of activating somatic mutations in the KRAS and BRAF genes on the res... BeFree 22442268 Detail
0.002 Malignant neoplasm of thyroid The effect of activating somatic mutations in the KRAS and BRAF genes on the res... BeFree 22442268 Detail
0.060 Thyroid carcinoma The effect of activating somatic mutations in the KRAS and BRAF genes on the res... BeFree 22442268 Detail
0.002 Thyroid carcinoma The effect of activating somatic mutations in the KRAS and BRAF genes on the res... BeFree 22442268 Detail
Annotation

Annotations

DescrptionSourceLinks
83 patients from a phase II trial (docetaxel + placebo or MEK1/2 inhibitor selumetinib) with KRAS mu... CIViC Evidence Detail
Preclinical study to investigate mechanisms of KRAS G12C activity and inhibition with ARS-853, a cov... CIViC Evidence Detail
In a study of 448 metastatic colorectal cancer patients treated with EGFR-TKIs and tested for EGFR a... CIViC Evidence Detail
In a study of 48 NSCLC patients, those with G12C or G12V mutant KRAS were associated with decreased ... CIViC Evidence Detail
In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring BRAF, KRAS, NRAS or PIK3CA mutat... CIViC Evidence Detail
In a retrospective study of 427 metastatic colorectal patients, KRAS mutations were observed in 43% ... CIViC Evidence Detail
In recurrent lung cancer patients treated with the epidermal growth factor receptor tyrosine kinase ... CIViC Evidence Detail
In a study of patients receiving melphalan-based therapy, those with KRAS codon 12 mutations were le... CIViC Evidence Detail
In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less s... CIViC Evidence Detail
In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less s... CIViC Evidence Detail
In in vitro experiments, myeloma cell lines expressing activating NRAS and KRAS mutations are less s... CIViC Evidence Detail
KRAS G12C occur more frequently in women than men. CIViC Evidence Detail
In an in vitro study, a SW48 cell line expressing KRAS G12C mutation demonstrated decreased sensitiv... CIViC Evidence Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Lung carcinoma ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Non-small cell lung carcinoma ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Endometrial carcinoma ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Thyroid tumor ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Neoplasm of ovary ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Lung adenocarcinoma ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Neoplasm of the large intestine ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Gallbladder cancer ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND not provided ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND RASopathy ClinVar Detail
NM_004985.5(KRAS):c.34G>T (p.Gly12Cys) AND Lung cancer ClinVar Detail
Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were identified in one NSC... DisGeNET Detail
Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were identified in one NSC... DisGeNET Detail
NA DisGeNET Detail
NA DisGeNET Detail
NA DisGeNET Detail
Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRA... DisGeNET Detail
The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of e... DisGeNET Detail
Presence of the KRAS G12C mutation had 96% specificity and positive predictive value for lung adenoc... DisGeNET Detail
Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRA... DisGeNET Detail
KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma. DisGeNET Detail
NA DisGeNET Detail
A KRAS G12S mutation was also evident in one sporadic schwannoma. DisGeNET Detail
NA DisGeNET Detail
Interestingly, during anti-EGFR treatment, it came to the selection of cells with KRAS G12C mutation... DisGeNET Detail
There was a strong association between germinal MUTYH mutation and KRAS Gly12Cys somatic mutation in... DisGeNET Detail
Follicular carcinoma presenting as autonomous functioning thyroid nodule and containing an activatin... DisGeNET Detail
There was 100% concordance between tissue and urinary cfDNA genotype in treatment-naïve samples. cfD... DisGeNET Detail
Follicular carcinoma presenting as autonomous functioning thyroid nodule and containing an activatin... DisGeNET Detail
The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of e... DisGeNET Detail
We selected NSCLC cell lines--A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H3122 (EML4-ALK E13;A20)... DisGeNET Detail
We have observed unusual transverse distal phalangeal creases in two patients, one with Costello syn... DisGeNET Detail
We have observed unusual transverse distal phalangeal creases in two patients, one with Costello syn... DisGeNET Detail
We have observed unusual transverse distal phalangeal creases in two patients, one with Costello syn... DisGeNET Detail
We have observed unusual transverse distal phalangeal creases in two patients, one with Costello syn... DisGeNET Detail
We have observed unusual transverse distal phalangeal creases in two patients, one with Costello syn... DisGeNET Detail
NA DisGeNET Detail
This system allowed us to rapidly compare the ability of 12 different KRAS mutations (G12A, G12C, G1... DisGeNET Detail
NA DisGeNET Detail
NA DisGeNET Detail
The effect of activating somatic mutations in the KRAS and BRAF genes on the responsiveness to sunit... DisGeNET Detail
The effect of activating somatic mutations in the KRAS and BRAF genes on the responsiveness to sunit... DisGeNET Detail
The effect of activating somatic mutations in the KRAS and BRAF genes on the responsiveness to sunit... DisGeNET Detail
The effect of activating somatic mutations in the KRAS and BRAF genes on the responsiveness to sunit... DisGeNET Detail

Overlapped Transcript Coordinates

Gene Transcript ID Exon Number Chromosome Start Stop Type Amino Mutation Transcript Position Links

Overlapped Transcript

Gene Transcript ID Chromosome Start Stop Links
Gene
-
dbSNP
rs121913530 dbSNP
Genome
hg19
Position
chr12:25,398,285-25,398,285
Variant Type
snv
Reference Allele
C
Alternative Allele
A
East Asian Chromosome Counts (ExAC)
7962
East Asian Allele Counts (ExAC)
1
East Asian Heterozygous Counts (ExAC)
1
East Asian Homozygous Counts (ExAC)
0
East Asian Allele Frequency (ExAC)
1.2559658377292137E-4
Chromosome Counts in All Race (ExAC)
101218
Allele Counts in All Race (ExAC)
2
Heterozygous Counts in All Race (ExAC)
2
Homozygous Counts in All Race (ExAC)
0
Allele Frequency in All Race (ExAC)
1.9759331344227312E-5
Variant (CIViC) (CIViC Variant)
G12C
Transcript 1 (CIViC Variant)
ENST00000256078.4
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/78
Summary (CIViC Variant)
While the KRAS G12 region is a widely studied recurrent region in cancer, its impact on clinical action is still debated. Often associated with tumors that are wild-type for other drivers (EGFR and ALK specifically), the prognosis for patients with this mutation seems to be worse than the KRAS wild-type cohort in patients with colorectal and pancreatic cancer, however this hypothesis is in need of further validation. This mutation, along with the mutations affecting the neighboring G13 position, may result in a less responsive tumor when treated with first-generation TKI's like gefitinib. However, cetuximab treatment was shown to extend survival in a cohort of colorectal patients.
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