chr2:29220829:G>T Detail (hg38) (ALK)

Information

Genome

Assembly Position
hg19 chr2:29,443,695-29,443,695 View the variant detail on this assembly version.
hg38 chr2:29,220,829-29,220,829

HGVS

Type Transcript Protein
RefSeq NM_004304.4:c.3522C>A NP_004295.2:p.Phe1174Leu
Ensemble ENST00000618119.4:c.2391C>A ENST00000618119.4:p.Phe797Leu
ENST00000642122.1:c.318C>A ENST00000642122.1:p.Phe106Leu
Summary

MGeND

Clinical significance Likely pathogenic Pathogenic
Variant entry 5
GWAS entry
Disease area statistics Show details

Frequency

[No Data.]

Prediction

ClinVar

Clinical Significance Pathogenic Likely pathogenic
Review star
Show details
Links
Type Database ID Link
Gene MIM 105590 OMIM
HGNC 427 HGNC
Ensembl ENSG00000171094 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC COSM28055 COSMIC
MONDO
Disease area statistics
MGeND
Clinical significance Last evaluated Condition Origin Submission ID Submitter Institute Citation Comment Image
Pathogenic neuroblastoma germline MGS000001
(TMGS000154) 		Kenjiro Kosaki Keio University
Likely pathogenic other unknown MGS000001
(TMGS000162) 		Kenjiro Kosaki Keio University
Likely pathogenic other somatic MGS000001
(TMGS000162) 		Kenjiro Kosaki Keio University
Likely pathogenic other unknown MGS000001
(TMGS000174) 		Kenjiro Kosaki Keio University
Likely pathogenic other somatic MGS000001
(TMGS000174) 		Kenjiro Kosaki Keio University
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2015-10-07 no assertion criteria provided Neuroblastoma, susceptibility to, 3 somatic Detail
not provided 2016-03-10 no assertion provided Non-small cell lung carcinoma somatic Detail
Likely pathogenic 2014-12-26 no assertion criteria provided lung adenocarcinoma somatic Detail
not provided 2016-03-10 no assertion provided Benign Soft Tissue Neoplasm of Uncertain Differentiation somatic Detail
Pathogenic 2016-03-10 no assertion criteria provided neuroblastoma somatic Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
neuroblastoma Crizotinib D Predictive Supports Resistance Somatic 3 22072639 Detail
neuroblastoma Crizotinib C Predictive Does Not Support Sensitivity/Response Somatic 3 23598171 Detail
neuroblastoma AZD3463 D Predictive Supports Sensitivity/Response Somatic 3 26786851 Detail
neuroblastoma Lorlatinib D Predictive Supports Sensitivity/Response Somatic 4 26554404 Detail
neuroblastoma TAE684 D Predictive Supports Sensitivity/Response Somatic 4 18923525 Detail
inflammatory myofibroblastic tumor Crizotinib D Predictive Supports Resistance Somatic 3 21030459 Detail
lung non-small cell carcinoma Crizotinib D Predictive Supports Resistance Somatic 3 21030459 Detail
neuroblastoma Alectinib D Predictive Supports Sensitivity/Response Somatic 3 21575866 Detail
neuroblastoma Crizotinib D Predictive Supports Sensitivity/Response Somatic 3 21948233 Detail
DisGeNET
[No Data.]
Annotation

Annotations

DescrptionSourceLinks
Cells lines expressing ALK harboring the F1174L mutation are less sensitive to growth inhibition by ... CIViC Evidence Detail
In a Phase I trial (NCT00939770) of the drug crizotinib in pediatric patients, a subset of 11 neurob... CIViC Evidence Detail
The SH-SY5Y neuroblastoma cell line containing the F1174L ALK mutation was found to undergo cell dea... CIViC Evidence Detail
Efficacy of the second generation ALK inhibitor PF-06463922 was tested on ALK mutation F1174L contai... CIViC Evidence Detail
SH-SY5Y and Kelly cells with mutant ALK (F1174L) and Ba/F3 cells overexpressing ALK harboring the F1... CIViC Evidence Detail
Ba/F3 cells expressing the RANBP2-ALK fusion containing an F1174L mutation were more resistant to cr... CIViC Evidence Detail
Ba/F3 cells expressing the EML4-ALK fusion containing an F1174L mutation were more resistant to criz... CIViC Evidence Detail
CH5424802 (Alectinib) is effective in inhibiting the activity of the F1174L ALK mutant in a kinase a... CIViC Evidence Detail
High levels of crizotinib can overcome drug resistance of Ba/F3 cells expressing the EML4-ALK fusion... CIViC Evidence Detail
NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu) AND Neuroblastoma, susceptibility to, 3 ClinVar Detail
NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu) AND Non-small cell lung carcinoma ClinVar Detail
NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu) AND Lung adenocarcinoma ClinVar Detail
NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu) AND Benign Soft Tissue Neoplasm of Uncertain Differentiati... ClinVar Detail
NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu) AND Neuroblastoma ClinVar 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
rs863225281 dbSNP
Genome
hg38
Position
chr2:29,220,829-29,220,829
Variant Type
snv
Reference Allele
G
Alternative Allele
T
Variant (CIViC) (CIViC Variant)
F1174L
Transcript 1 (CIViC Variant)
ENST00000389048.3
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/8
Summary (CIViC Variant)
ALK F1174L has been observed as recurrent in neuroblastoma, non-small cell lung cancer (NSCLC), and other cancer types. Neuroblastoma cells containing this mutation have shown resistance to low doses of criztonib. However, increased dosage can overcome this resistance in cell lines studies. TAE684 has also proven effective in both NSCLC and neuroblastoma F1174L containing cells.
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