chr2:29209798:C>T Detail (hg38) (ALK)

Information

Genome

Assembly Position
hg19 chr2:29,432,664-29,432,664 View the variant detail on this assembly version.
hg38 chr2:29,209,798-29,209,798

HGVS

Type Transcript Protein
RefSeq NM_004304.4:c.3824G>A NP_004295.2:p.Arg1275Gln
Ensemble ENST00000389048.8:c.3824G>A ENST00000389048.8:p.Arg1275Gln
ENST00000618119.4:c.2693G>A ENST00000618119.4:p.Arg898Gln
Summary

MGeND

Clinical significance Likely pathogenic Pathogenic
Variant entry 9
GWAS entry
Disease area statistics Show details

Frequency

[No Data.]

Prediction

ClinVar

Clinical Significance 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 COSM28056 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
(TMGS000174) 		Kenjiro Kosaki Keio University
Likely pathogenic other unknown MGS000001
(TMGS000174) 		Kenjiro Kosaki Keio University
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Pathogenic 2023-04-19 criteria provided, multiple submitters, no conflicts Neuroblastoma, susceptibility to, 3 germline somatic unknown Detail
Likely pathogenic 2016-05-31 no assertion criteria provided Breast neoplasm somatic Detail
Pathogenic 2016-05-31 no assertion criteria provided neuroblastoma somatic Detail
Likely pathogenic 2014-12-26 no assertion criteria provided Neoplasm of brain somatic Detail
Pathogenic 2020-10-23 criteria provided, single submitter not provided germline Detail
Pathogenic 2022-04-29 criteria provided, single submitter Hereditary cancer-predisposing syndrome germline Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
neuroblastoma Crizotinib C Predictive Supports Sensitivity/Response Rare Germline 2 23598171 Detail
neuroblastoma Crizotinib C Predictive Supports Sensitivity/Response Somatic 2 23598171 Detail
neuroblastoma Lorlatinib D Predictive Supports Sensitivity/Response Somatic 4 26554404 Detail
neuroblastoma Crizotinib D Predictive Supports Sensitivity/Response Somatic 3 22072639 Detail
neuroblastoma TAE684 D Predictive Supports Sensitivity/Response Somatic 3 18923525 Detail
neuroblastoma TAE684 D Predictive Supports Resistance Somatic 3 18923525 Detail
DisGeNET
Score Disease name Description Source Pubmed Links
0.023 Central neuroblastoma Activating mutations within the full-length ALK kinase domain, most commonly R12... BeFree 20632993 Detail
0.279 neuroblastoma Activating mutations within the full-length ALK kinase domain, most commonly R12... BeFree 20632993 Detail
0.240 Neuroblastoma, susceptibility to, 3 NA CLINVAR Detail
0.080 Central neuroblastoma The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tum... BeFree 24947326 Detail
0.334 neuroblastoma The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tum... BeFree 24947326 Detail
0.010 Carcinogenesis The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tum... BeFree 24947326 Detail
Annotation

Annotations

DescrptionSourceLinks
This Phase I study of crizotinib involved a cohort of pediatric neuroblastoma patients between ages ... CIViC Evidence Detail
A cohort of pediatric neuroblastoma patients ages 12 months to 22 years were assessed for response t... CIViC Evidence Detail
In NB-1643 and LAN-5 neuroblastoma cell lines containing R1275Q mutation, PF-06463922 showed 51 and ... CIViC Evidence Detail
Cells lines expressing ALK harboring the F1174L mutation are less sensitive to growth inhibition by ... CIViC Evidence Detail
TAE684 inhibits growth of Ba/F3 cells expressing ALK mutations; however, cells with the R1275Q mutat... CIViC Evidence Detail
The SMS-KCNR cell line harboring the R1275Q mutation was resistant to TAE684. CIViC Evidence Detail
NM_004304.5(ALK):c.3824G>A (p.Arg1275Gln) AND Neuroblastoma, susceptibility to, 3 ClinVar Detail
NM_004304.5(ALK):c.3824G>A (p.Arg1275Gln) AND Breast neoplasm ClinVar Detail
NM_004304.5(ALK):c.3824G>A (p.Arg1275Gln) AND Neuroblastoma ClinVar Detail
NM_004304.5(ALK):c.3824G>A (p.Arg1275Gln) AND Neoplasm of brain ClinVar Detail
NM_004304.5(ALK):c.3824G>A (p.Arg1275Gln) AND not provided ClinVar Detail
NM_004304.5(ALK):c.3824G>A (p.Arg1275Gln) AND Hereditary cancer-predisposing syndrome ClinVar Detail
Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, whic... DisGeNET Detail
Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, whic... DisGeNET Detail
NA DisGeNET Detail
The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse ... DisGeNET Detail
The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse ... DisGeNET Detail
The two most frequent mutations, ALK-F1174L and ALK-R1275Q, contribute to NB tumorigenesis in mouse ... 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
rs113994087 dbSNP
Genome
hg38
Position
chr2:29,209,798-29,209,798
Variant Type
snv
Reference Allele
C
Alternative Allele
T
Variant (CIViC) (CIViC Variant)
R1275Q
Transcript 1 (CIViC Variant)
ENST00000389048.3
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/9
Summary (CIViC Variant)
ALK R1275Q has been observed as a recurrent mutation in neuroblastoma, non-small cell lung cancer (NSCLC), as well as other cancer types. Neuroblastoma cells with this mutation have shown sensitivity to the ALK-inhibitor TAE684. This and the geldanamycin deriviative 17-DMAG have been shown to be effective in NSCLC cell lines.
Genome browser