rs2227984

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005228.5(EGFR):c.1887T>A(p.Thr629Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,613,896 control chromosomes in the GnomAD database, including 103,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T629T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.34 ( 9180 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93898 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.663

Publications

53 publications found

Variant links:

Genes affected

EGFR (HGNC:3236): (epidermal growth factor receptor) The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor, thus inducing receptor dimerization and tyrosine autophosphorylation leading to cell proliferation. Mutations in this gene are associated with lung cancer. EGFR is a component of the cytokine storm which contributes to a severe form of Coronavirus Disease 2019 (COVID-19) resulting from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). [provided by RefSeq, Jul 2020]

EGFR Gene-Disease associations (from GenCC):

lung cancer
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
non-small cell lung carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
inflammatory skin and bowel disease, neonatal, 2
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
neonatal inflammatory skin and bowel disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EGFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-55171181-T-A is Benign according to our data. Variant chr7-55171181-T-A is described in ClinVar as Benign. ClinVar VariationId is 259677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.663 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.1887T>A	p.Thr629Thr	synonymous_variant	Exon 16 of 28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7 link	c.1887T>A	p.Thr629Thr	synonymous_variant	Exon 16 of 28	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51789

AN:

152040

Hom.:

9181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.552

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.367

GnomAD2 exomes

AF:

0.376

AC:

94569

AN:

251376

AF XY:

0.380

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.483

Gnomad EAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.353

AC:

516104

AN:

1461738

Hom.:

93898

Cov.:

AF XY:

0.356

AC XY:

258718

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.278

AC:

9311

AN:

33480

American (AMR)

AF:

0.393

AC:

17560

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

12736

AN:

26132

East Asian (EAS)

AF:

0.603

AC:

23929

AN:

39696

South Asian (SAS)

AF:

0.424

AC:

36605

AN:

86252

European-Finnish (FIN)

AF:

0.328

AC:

17489

AN:

53382

Middle Eastern (MID)

AF:

0.465

AC:

2679

AN:

5764

European-Non Finnish (NFE)

AF:

0.335

AC:

372880

AN:

1111920

Other (OTH)

AF:

0.379

AC:

22915

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18734

37469

56203

74938

93672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12158

24316

36474

48632

60790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.340

AC:

51801

AN:

152158

Hom.:

9180

Cov.:

AF XY:

0.345

AC XY:

25637

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.280

AC:

11637

AN:

41496

American (AMR)

AF:

0.366

AC:

5607

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

1656

AN:

3468

East Asian (EAS)

AF:

0.553

AC:

2855

AN:

5160

South Asian (SAS)

AF:

0.440

AC:

2122

AN:

4826

European-Finnish (FIN)

AF:

0.331

AC:

3510

AN:

10592

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.341

AC:

23191

AN:

67996

Other (OTH)

AF:

0.368

AC:

778

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1772

3544

5317

7089

8861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.358

Hom.:

3333

Bravo

AF:

0.345

Asia WGS

AF:

0.480

AC:

1668

AN:

3478

EpiCase

AF:

0.364

EpiControl

AF:

0.360

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 07, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

EGFR-related lung cancer

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Oct 18, 2024

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Lung cancer

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inflammatory skin and bowel disease, neonatal, 2

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.22

(source)

DANN

Benign

0.73

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over