NM_005228.5(EGFR):c.2497_2498delinsCC (p.Leu833Pro) AND EGFR-related lung cancer

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 23, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001919602.3

Allele description [Variation Report for NM_005228.5(EGFR):c.2497_2498delinsCC (p.Leu833Pro)]

NM_005228.5(EGFR):c.2497_2498delinsCC (p.Leu833Pro)

Gene:

EGFR:epidermal growth factor receptor [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

7p11.2

Genomic location:

Preferred name:

NM_005228.5(EGFR):c.2497_2498delinsCC (p.Leu833Pro)

HGVS:

NC_000007.14:g.55191746_55191747delinsCC
NG_007726.3:g.177715_177716delinsCC
NM_001346897.2:c.2362_2363delinsCC
NM_001346898.2:c.2497_2498delinsCC
NM_001346899.2:c.2362_2363delinsCC
NM_001346900.2:c.2338_2339delinsCC
NM_001346941.2:c.1696_1697delinsCC
NM_005228.5:c.2497_2498delinsCCMANE SELECT
NP_001333826.1:p.Leu788Pro
NP_001333827.1:p.Leu833Pro
NP_001333828.1:p.Leu788Pro
NP_001333829.1:p.Leu780Pro
NP_001333870.1:p.Leu566Pro
NP_005219.2:p.Leu833Pro
LRG_304:g.177715_177716delinsCC
NC_000007.13:g.55259439_55259440delinsCC

Protein change:

L566P

Links:

dbSNP: rs2128964422

NCBI 1000 Genomes Browser:

rs2128964422

Molecular consequence:

NM_001346897.2:c.2362_2363delinsCC - missense variant - [Sequence Ontology: SO:0001583]
NM_001346898.2:c.2497_2498delinsCC - missense variant - [Sequence Ontology: SO:0001583]
NM_001346899.2:c.2362_2363delinsCC - missense variant - [Sequence Ontology: SO:0001583]
NM_001346900.2:c.2338_2339delinsCC - missense variant - [Sequence Ontology: SO:0001583]
NM_001346941.2:c.1696_1697delinsCC - missense variant - [Sequence Ontology: SO:0001583]
NM_005228.5:c.2497_2498delinsCC - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: EGFR-related lung cancer (EGFR)
Identifiers:: MedGen: CN130014

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002193145	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 23, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002193145

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 23, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002193145.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces leucine with proline at codon 833 of the EGFR protein (p.Leu833Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This variant has not been reported in the literature in individuals affected with EGFR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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