NM_020631.6(PLEKHG5):c.2902del (p.Val968fs) AND multiple conditions

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 28, 2024
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:: RCV002587493.5

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.2902del (p.Val968fs)]

NM_020631.6(PLEKHG5):c.2902del (p.Val968fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1p36.31

Genomic location:

Preferred name:

NM_020631.6(PLEKHG5):c.2902del (p.Val968fs)

HGVS:

NC_000001.11:g.6467936del
NG_007978.1:g.57076del
NG_029910.1:g.3262del
NM_001042663.3:c.3013del
NM_001042664.2:c.2902del
NM_001042665.2:c.2902del
NM_001265592.2:c.3013del
NM_001265593.2:c.3109del
NM_001265594.3:c.2738-36del
NM_020631.6:c.2902delMANE SELECT
NM_198681.4:c.2902del
NP_001036128.2:p.Val1005fs
NP_001036129.1:p.Val968Serfs
NP_001036129.1:p.Val968fs
NP_001036130.1:p.Val968Serfs
NP_001036130.1:p.Val968fs
NP_001252521.2:p.Val1005fs
NP_001252522.1:p.Val1037Serfs
NP_001252522.1:p.Val1037fs
NP_065682.2:p.Val968Serfs
NP_065682.2:p.Val968fs
NP_941374.3:p.Val968fs
LRG_262t1:c.2900del
LRG_262:g.57076del
LRG_262p1:p.Val968Serfs
NC_000001.10:g.6527994del
NC_000001.10:g.6527996del
NM_001042664.1:c.2900delG
NM_001042665.1:c.2900delG
NM_001265593.1:c.3107delG
NM_020631.3:c.2900delG

Protein change:

V1005fs

Links:

dbSNP: rs773188120

NCBI 1000 Genomes Browser:

rs773188120

Molecular consequence:

NM_001042663.3:c.3013del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042664.2:c.2902del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001042665.2:c.2902del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001265592.2:c.3013del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001265593.2:c.3109del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020631.6:c.2902del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_198681.4:c.2902del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001265594.3:c.2738-36del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV002948138	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17564964, 23777631, 28492532
SCV005659015	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 28, 2024)	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

SCV002948138

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005659015

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 28, 2024)

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

The nuclear factor kappaB-activator gene PLEKHG5 is mutated in a form of autosomal recessive lower motor neuron disease with childhood onset.

Maystadt I, Rezsöhazy R, Barkats M, Duque S, Vannuffel P, Remacle S, Lambert B, Najimi M, Sokal E, Munnich A, Viollet L, Verellen-Dumoulin C.

Am J Hum Genet. 2007 Jul;81(1):67-76. Epub 2007 May 16.

PubMed [citation]

PMID:: 17564964
PMCID:: PMC1950913

PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

Azzedine H, Zavadakova P, Planté-Bordeneuve V, Vaz Pato M, Pinto N, Bartesaghi L, Zenker J, Poirot O, Bernard-Marissal N, Arnaud Gouttenoire E, Cartoni R, Title A, Venturini G, Médard JJ, Makowski E, Schöls L, Claeys KG, Stendel C, Roos A, Weis J, Dubourg O, Leal Loureiro J, et al.

Hum Mol Genet. 2013 Oct 15;22(20):4224-32. doi: 10.1093/hmg/ddt274. Epub 2013 Jun 17.

PubMed [citation]

PMID:: 23777631
PMCID:: PMC3983407

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002948138.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. This variant is present in population databases (rs773188120, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Val968Serfs*16) in the PLEKHG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PLEKHG5 are known to be pathogenic (PMID: 17564964, 23777631).

#	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

From Fulgent Genetics, Fulgent Genetics, SCV005659015.1

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

#	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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