NM_016341.4(PLCE1):c.4724G>A (p.Arg1575Gln) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 28, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000594173.5

Allele description [Variation Report for NM_016341.4(PLCE1):c.4724G>A (p.Arg1575Gln)]

NM_016341.4(PLCE1):c.4724G>A (p.Arg1575Gln)

Genes:

PLCE1-AS1:PLCE1 antisense RNA 1 [Gene - HGNC]
PLCE1:phospholipase C epsilon 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.33

Genomic location:

Preferred name:

NM_016341.4(PLCE1):c.4724G>A (p.Arg1575Gln)

HGVS:

NC_000010.11:g.94279840G>A
NG_015799.1:g.290852G>A
NM_001165979.2:c.3800G>A
NM_001288989.2:c.4676G>A
NM_016341.4:c.4724G>AMANE SELECT
NP_001159451.1:p.Arg1267Gln
NP_001275918.1:p.Arg1559Gln
NP_057425.3:p.Arg1575Gln
NC_000010.10:g.96039597G>A
NM_016341.3:c.4724G>A
NR_033969.1:n.858C>T

Protein change:

R1267Q

Links:

dbSNP: rs2274224

NCBI 1000 Genomes Browser:

rs2274224

Molecular consequence:

NM_001165979.2:c.3800G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288989.2:c.4676G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016341.4:c.4724G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033969.1:n.858C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000708414	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (May 8, 2017)	germline	clinical testing	Citation Link,
SCV004677689	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 28, 2023)	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

SCV000708414

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(May 8, 2017)

germline

clinical testing

Citation Link,

SCV004677689

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 28, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Eurofins Ntd Llc (ga), SCV000708414.2

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

#	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		1	not provided	not provided	not provided

From Invitae, SCV004677689.1

#	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1575 of the PLCE1 protein (p.Arg1575Gln). This variant is present in population databases (rs2274224, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PLCE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 501892). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PLCE1 protein function with a negative predictive value of 80%. 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: Mar 5, 2024

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