rs2227984

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005228.5(EGFR):​c.1887T>A​(p.Thr629=) 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 (★★).

Frequency

Genomes: 𝑓 0.34 ( 9180 hom., cov: 33)
Exomes 𝑓: 0.35 ( 93898 hom. )

Consequence

EGFR
NM_005228.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.663
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-55171181-T-A is described in Lovd as [Benign].
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/exons MANE Protein UniProt
EGFRNM_005228.5 linkuse as main transcriptc.1887T>A p.Thr629= synonymous_variant 16/28 ENST00000275493.7 NP_005219.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EGFRENST00000275493.7 linkuse as main transcriptc.1887T>A p.Thr629= synonymous_variant 16/281 NM_005228.5 ENSP00000275493 P1P00533-1
EGFRENST00000455089.5 linkuse as main transcriptc.1752T>A p.Thr584= synonymous_variant 15/261 ENSP00000415559
EGFRENST00000450046.2 linkuse as main transcriptc.1728T>A p.Thr576= synonymous_variant 16/284 ENSP00000413354
EGFRENST00000700145.1 linkuse as main transcriptc.237T>A p.Thr79= synonymous_variant 3/9 ENSP00000514824

Frequencies

GnomAD3 genomes
AF:
0.341
AC:
51789
AN:
152040
Hom.:
9181
Cov.:
33
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
GnomAD3 exomes
AF:
0.376
AC:
94569
AN:
251376
Hom.:
18426
AF XY:
0.380
AC XY:
51581
AN XY:
135860
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 SAS exome
AF:
0.423
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.:
44
AF XY:
0.356
AC XY:
258718
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.278
Gnomad4 AMR exome
AF:
0.393
Gnomad4 ASJ exome
AF:
0.487
Gnomad4 EAS exome
AF:
0.603
Gnomad4 SAS exome
AF:
0.424
Gnomad4 FIN exome
AF:
0.328
Gnomad4 NFE exome
AF:
0.335
Gnomad4 OTH exome
AF:
0.379
GnomAD4 genome
AF:
0.340
AC:
51801
AN:
152158
Hom.:
9180
Cov.:
33
AF XY:
0.345
AC XY:
25637
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.280
Gnomad4 AMR
AF:
0.366
Gnomad4 ASJ
AF:
0.478
Gnomad4 EAS
AF:
0.553
Gnomad4 SAS
AF:
0.440
Gnomad4 FIN
AF:
0.331
Gnomad4 NFE
AF:
0.341
Gnomad4 OTH
AF:
0.368
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:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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 -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 07, 2019- -
EGFR-related lung cancer Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Lung cancer Benign:1
Benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -
Inflammatory skin and bowel disease, neonatal, 2 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 30, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.22
DANN
Benign
0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2227984; hg19: chr7-55238874; COSMIC: COSV51770406; COSMIC: COSV51770406; API