NM_020631.6(PLEKHG5):c.1542+1G>C AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 16, 2023
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:: RCV003805294.4

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.1542+1G>C]

NM_020631.6(PLEKHG5):c.1542+1G>C

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.1542+1G>C

HGVS:

NC_000001.11:g.6470734C>G
NG_007978.1:g.54276G>C
NG_029910.1:g.462G>C
NM_001042663.3:c.1653+1G>C
NM_001042664.2:c.1542+1G>C
NM_001042665.2:c.1542+1G>C
NM_001265592.2:c.1653+1G>C
NM_001265593.2:c.1749+1G>C
NM_001265594.3:c.1542+1G>C
NM_020631.6:c.1542+1G>CMANE SELECT
NM_198681.4:c.1542+1G>C
LRG_262:g.54276G>C
NC_000001.10:g.6530794C>G

Links:

dbSNP: rs1644545351

Molecular consequence:

NM_001042663.3:c.1653+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001042664.2:c.1542+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001042665.2:c.1542+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001265592.2:c.1653+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001265593.2:c.1749+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001265594.3:c.1542+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_020631.6:c.1542+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_198681.4:c.1542+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV004593055	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 16, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 17564964, 23777631, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004593055

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 16, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004593055.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 14 of the PLEKHG5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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

Last Updated: Apr 12, 2026

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