NM_020631.6(PLEKHG5):c.2234C>G (p.Pro745Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 15, 2022
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:: RCV002725350.4

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.2234C>G (p.Pro745Arg)]

NM_020631.6(PLEKHG5):c.2234C>G (p.Pro745Arg)

Gene:

PLEKHG5:pleckstrin homology and RhoGEF domain containing G5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.31

Genomic location:

Preferred name:

NM_020631.6(PLEKHG5):c.2234C>G (p.Pro745Arg)

HGVS:

NC_000001.11:g.6469057G>C
NG_007978.1:g.55953C>G
NG_029910.1:g.2139C>G
NM_001042663.3:c.2345C>G
NM_001042664.2:c.2234C>G
NM_001042665.2:c.2234C>G
NM_001265592.2:c.2345C>G
NM_001265593.2:c.2441C>G
NM_001265594.3:c.2234C>G
NM_020631.6:c.2234C>GMANE SELECT
NM_198681.4:c.2234C>G
NP_001036128.2:p.Pro782Arg
NP_001036129.1:p.Pro745Arg
NP_001036129.1:p.Pro745Arg
NP_001036130.1:p.Pro745Arg
NP_001036130.1:p.Pro745Arg
NP_001252521.2:p.Pro782Arg
NP_001252522.1:p.Pro814Arg
NP_001252522.1:p.Pro814Arg
NP_001252523.1:p.Pro745Arg
NP_001252523.1:p.Pro745Arg
NP_065682.2:p.Pro745Arg
NP_065682.2:p.Pro745Arg
NP_941374.3:p.Pro745Arg
LRG_262t1:c.2234C>G
LRG_262:g.55953C>G
LRG_262p1:p.Pro745Arg
NC_000001.10:g.6529117G>C
NM_001042664.1:c.2234C>G
NM_001042665.1:c.2234C>G
NM_001265593.1:c.2441C>G
NM_001265594.2:c.2234C>G
NM_020631.3:c.2234C>G

Protein change:

P745R

Links:

dbSNP: rs536038159

NCBI 1000 Genomes Browser:

rs536038159

Molecular consequence:

NM_001042663.3:c.2345C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042664.2:c.2234C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042665.2:c.2234C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265592.2:c.2345C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265593.2:c.2441C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001265594.3:c.2234C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020631.6:c.2234C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198681.4:c.2234C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronopathy, distal hereditary motor, autosomal recessive 4
Synonyms:: Autosomal recessive lower motor neuron disease with childhood onset; NEUROPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL RECESSIVE 4
Identifiers:: MONDO: MONDO:0012608; MedGen: C1970211; Orphanet: 206580; OMIM: 611067

Name:: Charcot-Marie-Tooth disease recessive intermediate C
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, RECESSIVE INTERMEDIATE C
Identifiers:: MONDO: MONDO:0014154; MedGen: C3809309; Orphanet: 369867; OMIM: 615376

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002995341	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 15, 2022)	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

SCV002995341

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 15, 2022)

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	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002995341.3

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

Description

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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. This variant is present in population databases (rs536038159, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 745 of the PLEKHG5 protein (p.Pro745Arg).

#	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: May 16, 2025

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