VCV000045225.7 - ClinVar

NM_005228.5(EGFR):c.2156G>C (p.Gly719Ala)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(5)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

Oncogenicity

The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate oncogenicity classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Oncogenic

criteria provided, single submitter

Variant Details

Identifiers

NM_005228.5(EGFR):c.2156G>C (p.Gly719Ala)

Variation ID: 45225 Accession: VCV000045225.7

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7p11.2 7: 55174015 (GRCh38) [ NCBI UCSC ] 7: 55241708 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 31, 2015	May 11, 2022	Jan 4, 2013
Somatic - Oncogenicity	Aug 11, 2024	Aug 11, 2024	Jul 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_005228.5:c.2156G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005219.2:p.Gly719Ala	missense
NM_001346897.2:c.2021G>C	NP_001333826.1:p.Gly674Ala	missense
NM_001346898.2:c.2156G>C	NP_001333827.1:p.Gly719Ala	missense
NM_001346899.2:c.2021G>C	NP_001333828.1:p.Gly674Ala	missense
NM_001346900.2:c.1997G>C	NP_001333829.1:p.Gly666Ala	missense
NM_001346941.2:c.1355G>C	NP_001333870.1:p.Gly452Ala	missense
NC_000007.14:g.55174015G>C
NC_000007.13:g.55241708G>C
NG_007726.3:g.159984G>C
LRG_304:g.159984G>C
LRG_304t1:c.2156G>C
	P00533:p.Gly719Ala

... more HGVS ... less HGVS

Protein change

G719A, G666A, G674A, G452A

Other names

Canonical SPDI

NC_000007.14:55174014:G:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA135775 UniProtKB: P00533#VAR_026086 dbSNP: rs121913428 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
EGFR		No evidence available	No evidence available	GRCh38 GRCh37	2678	3032

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Non-small cell lung carcinoma	Pathogenic (3)	criteria provided, single submitter	Jan 4, 2013	RCV000038381.7
Lung adenocarcinoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000436293.1
Glioblastoma	Likely pathogenic (1)	no assertion criteria provided	May 31, 2016	RCV000426037.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 04, 2013)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	Non-Small Cell Lung Cancer Affected status: not provided Allele origin: somatic	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000062053.3 First in ClinVar: May 03, 2013 Last updated: Jan 31, 2015	Publications: PubMed (4) PubMed: 15710947‚ 15738541‚ 20479403‚ 21531810 Comment: The Gly719Ala variant has been reported in isolation in individuals with increased sensitivity to gefitinib treatment (Han 2005). Number of individuals with the variant: 30
Pathogenic (-)	no assertion criteria provided Method: curation	Non-small cell lung carcinoma Affected status: yes Allele origin: germline	Molecular Diagnostics Laboratory, University of Rochester Medical Center Accession: SCV002506983.1 First in ClinVar: May 11, 2022 Last updated: May 11, 2022	Publications: PubMed (1) PubMed: 31396478
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	Glioblastoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504235.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000275493:c.2156G>C
Pathogenic (Jul 14, 2015)	no assertion criteria provided Method: literature only	Non-small cell lung carcinoma (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504234.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (14) PubMed: 16011858‚ 20479403‚ 19922469‚ 15710947‚ 2302402‚ 15329413‚ 23242437‚ 15118073‚ 15118125‚ 18458038‚ 25157968‚ 22753918‚ 23102728‚ 16115929 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000275493:c.2156G>C
Likely pathogenic (May 31, 2016)	no assertion criteria provided Method: literature only	None (Somatic mutation) Affected status: yes Allele origin: somatic	Database of Curated Mutations (DoCM) Accession: SCV000504236.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Publications: PubMed (1) PubMed: 26619011 Other databases http://docm.genome.wustl.edu/var… http://docm.genome.wustl.edu/variants/ENST00000275493:c.2156G>C

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Afatinib for Advanced Non-small Cell Lung Cancer in a Case With an Uncommon Epidermal Growth Factor Receptor Mutation (G719A) Identified in the Cerebrospinal Fluid.	Ma C	Frontiers in oncology	2019	PMID: 31396478
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.	Chang MT	Nature biotechnology	2016	PMID: 26619011
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.	MacConaill LE	The Journal of molecular diagnostics : JMD	2014	PMID: 25157968
Compound EGFR mutations and response to EGFR tyrosine kinase inhibitors.	Kobayashi S	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer	2013	PMID: 23242437
MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib.	Huang MH	Molecular oncology	2013	PMID: 23102728
Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer.	Ramalingam SS	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2012	PMID: 22753918
Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer.	Wu JY	Clinical cancer research : an official journal of the American Association for Cancer Research	2011	PMID: 21531810
Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer.	Sequist LV	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2010	PMID: 20479403
Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer.	Mitsudomi T	The FEBS journal	2010	PMID: 19922469
First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations.	Sequist LV	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2008	PMID: 18458038
Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas.	Taron M	Clinical cancer research : an official journal of the American Association for Cancer Research	2005	PMID: 16115929
Mutations in the tyrosine kinase domain of the EGFR gene associated with gefitinib response in non-small-cell lung cancer.	Rosell R	Lung cancer (Amsterdam, Netherlands)	2005	PMID: 16011858
Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence.	Mitsudomi T	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2005	PMID: 15738541
Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib.	Han SW	Journal of clinical oncology : official journal of the American Society of Clinical Oncology	2005	PMID: 15710947
EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.	Pao W	Proceedings of the National Academy of Sciences of the United States of America	2004	PMID: 15329413
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.	Paez JG	Science (New York, N.Y.)	2004	PMID: 15118125
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.	Lynch TJ	The New England journal of medicine	2004	PMID: 15118073
Effects of marine oil-enriched diets on guinea pig megakaryocyte and platelet lipids: effects on thromboxane synthesis and platelet function.	Schick PK	Biochimica et biophysica acta	1990	PMID: 2302402
http://docm.genome.wustl.edu/variants/ENST00000275493:c.2156G>C	-	-	-	-
click to load more click to collapse

Conditions - Somatic

Tumor type Help The tumor type for this variant-condition (RCV) record in ClinVar.	Clinical impact (# of submissions) Help The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Oncogenicity Help The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the tumor type.	Variation/condition record Help The most recent date that a submitter evaluated this variant for the tumor type.
Neoplasm		Oncogenic criteria provided, single submitter	Jul 31, 2024	RCV004668759.1

Submissions - Somatic

Oncogenicity Help The submitted oncogenicity classification for each SCV record. (Last evaluated)	Review Status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Tumor type Help The tumor type for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.

Oncogenic

(Jul 31, 2024)

(ClinGen/CGC/VICC Guidelines for Oncogenicity, 2022)

Method: clinical testing

Neoplasm

Affected status: unknown

Allele origin: somatic

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Accession: SCV005094133.1
First In ClinVar: Aug 11, 2024
Last updated: Aug 11, 2024

Citations for somatic classification of this variant

There are no citations for somatic classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs121913428 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 11, 2024

ClinVar Genomic variation as it relates to human health

NM_005228.5(EGFR):c.2156G>C (p.Gly719Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Conditions - Somatic

Submissions - Somatic

Citations for somatic classification of this variant

Text-mined citations for rs121913428 ...