chr17:39724744:>TACGTGATGGCT Detail (hg38) (ERBB2)

Information

Genome

Assembly Position
hg19 chr17:37,880,997-37,880,997 
hg38 chr17:39,724,744-39,724,744

HGVS

Type Transcript Protein
RefSeq NM_004448.3:c.2325_2326insTACGTGATGGCT NP_004439.2:p.Tyr772_Ala775dup
NM_001289937.1:c.2325_2326insTACGTGATGGCT NP_001276866.1:p.Tyr772_Ala775dup
NM_001005862.2:c.2235_2236insTACGTGATGGCT NP_001005862.1:p.Tyr742_Ala745dup
Summary

MGeND

Clinical significance
Variant entry
GWAS entry
Disease area statistics Show details

Frequency

[No Data.]

Prediction

ClinVar

Clinical Significance Likely pathogenic
Review star
Show details
Links
Type Database ID Link
Gene MIM 164870 OMIM
HGNC 3430 HGNC
Ensembl ENSG00000141736 Ensembl
NCBI NCBI
Gene Cards Gene Cards
OncoKB OncoKB
Type Database ID Link
Variant TogoVar
COSMIC
MONDO
Disease area statistics
[No Data.]
MGeND
[No Data.]
ClinVar
Clinical significance Last evaluated Review status Condition Origin Links
Likely pathogenic 2011-03-11 criteria provided, single submitter Non-small cell lung carcinoma somatic Detail
Likely pathogenic no assertion criteria provided lung adenocarcinoma somatic Detail
CIViC
Disease Drug EL ET ED CS VO TR Pubmed Links
lung adenocarcinoma Afatinib C Predictive Supports Sensitivity/Response Somatic 4 26559459 Detail
lung carcinoma Afatinib D Predictive Supports Sensitivity/Response Somatic 4 19122144 Detail
lung adenocarcinoma Trastuzumab Emtansine C Predictive Supports Sensitivity/Response Somatic 3 25789838 Detail
lung adenocarcinoma Afatinib C Predictive Supports Sensitivity/Response Somatic 3 22325357 Detail
lung non-small cell carcinoma Dacomitinib B Predictive Does Not Support Sensitivity/Response Somatic 2 25899785 Detail
lung non-small cell carcinoma Sirolimus,Afatinib D Predictive Supports Sensitivity/Response Somatic 3 19122144 Detail
DisGeNET
[No Data.]
Annotation

Annotations

DescrptionSourceLinks
A 55 year old heavily pretreated patient with equivocal HER2 overexpression (IHC2+ and no amplificat... CIViC Evidence Detail
Human HER2 with YVMA insertion was put under a clara cell specific, rtTA promoter system inducible v... CIViC Evidence Detail
A 51-year old female never smoker with stage IV lung adenocarcinoma carrying a HER2 insertion in exo... CIViC Evidence Detail
A Phase II study for use of Afatinib in non- or light smokers with lung adenocarcinoma. Three patien... CIViC Evidence Detail
Phase 2 trial of ERBB-inhibitor dacomitinib in stage IIIB/IV lung cancers with HER2 mutations or amp... CIViC Evidence Detail
In preclinical studies of transgenic mice and xenografts, continuous expression of mutant ERBB2 (M77... CIViC Evidence Detail
NM_004448.4(ERBB2):c.2314_2325dup (p.Tyr772_Ala775dup) AND Non-small cell lung carcinoma ClinVar Detail
NM_004448.4(ERBB2):c.2314_2325dup (p.Tyr772_Ala775dup) AND Lung adenocarcinoma 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
rs397516977 dbSNP
Genome
hg38
Position
chr17:39,724,744-39,724,744
Variant Type
snv
Reference Allele
-
Alternative Allele
TACGTGATGGCT
Variant (CIViC) (CIViC Variant)
Y772_A775DUP
Transcript 1 (CIViC Variant)
ENST00000269571.5
Variant URL (CIViC Variant)
https://civic.genome.wustl.edu/links/variants/414
Summary (CIViC Variant)
Mutations in the HER2 kinase domain occur at a 2-4% frequency in lung adenocarcinomas, the majority of which are in exon 20 as in-frame duplications or insertions in a small 8 codon region (774-781 or 775-782). These are analogous to the exon 20 alterations found in EGFR TK domain. The M774 insertion, M774insAYVM, represents 62.5% of all HER2 kinase domain mutations identified (when combined with the A775insYVMA mutations as they translate to the identical amino acid sequence changes). As demonstrated in mouse models (Perrera et al., PNAS 2009) and subsequent clinical trials in human lung adenocarcinoma with these insertions, HER2 YVMA mutants predict response to several targeted HER2 agonists such as afatinib, trastuzumab, neratinib and TDM-1 (trastuzumab emtansine) as monotherapy or combined with specific chemotherapies.
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